Therapeutic methods using fusion proteins between interleukin-3 (IL-3) variants and other hematopoietic factors

A method of treating a patient having a hematopoietic disorder comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of mematopoietic cells int the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, -R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a patient having a hematopoietic disorder comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly,. Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a patient having a hematopoietic disorder comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

A method of treating a patient comprising the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a human interleukin-3 mutant amino acid sequence as shown in SEQ ID NO:
• 1,
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a patient comprising the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a patient comprising the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val,. Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a patient comprising the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a human interleukin-3 mutant amino acid sequence as shown in SEQ ID NO:

• 1,
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser,. Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient comprising administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein comprising a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

A method of treating a patient having a hematopoietic disorder consisting of administering to the patient a fusion protein in an amount effective to promote the growth of differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, -R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a patient having a hematopoietic disorder consisting of administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a patient having a hematopoietic disorder consisting of administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

A method of treating a patient consisting of the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a patient consisting of the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His,. Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a patient consisting of the steps of:

• (i) administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:
• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2
• (ii) removing hematopoietic cells from said patient;
• (iii) administering cancer radiation therapy or chemotherapy to said patient;
• and
• (iv) returning said hematopoietic cells to said patient.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient consisting of administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.2 is a human interleukin-3 mutant polypeptide sequence of SEQ ID NO:1;
• wherein
• Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg,. Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp;
• Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 103 is Asp, or Ser;
• Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp;
• Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys;
• Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, an interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient consisting of administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:4;
• wherein
• Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly;
• Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;
• Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 22 is Asp, Leu, or Val;
• Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 24 is Asn, or Ala;
• Xaa at position 26 is Leu, Trp, or Arg;
• Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;
• Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met;
• Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;
• Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 43 is Asn or Gly;
• Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;
• Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;
• Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 71 is Leu, Asn, Val, or Gln;
• Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 73 is Leu, Ser, Trp, or Gly;
• Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
• Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
• Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro;
• Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr;
• Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
• Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
• Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;
• Xaa at position 87 is Asp;
• Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
• Xaa at position 89 is Asp, or Ser;
• Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
• Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
• Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;
• Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;
• Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;
• Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
• Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
• Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
• Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
• Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;
• Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• and
• Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 3 of the amino acids designated by Xaa are different from the corresponding native amino acids of (1-133) human interleukin-3;
• and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.

A method of treating a side effect of cancer chemotherapy or radiation therapy in a patient consisting of administering to the patient a fusion protein in an amount effective to promote the growth or differentiation of hematopoietic cells in the patient, the fusion protein consisting of a polypeptide having a formula selected from the group consisting of:

• R.sub.1 -L-R.sub.2, R.sub.2 -L-R.sub.1, R.sub.1 -R.sub.2, R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -L-R.sub.2, Met-Ala-R.sub.2 -L-R.sub.1, Met-Ala-R.sub.1 -R.sub.2, Met-Ala-R.sub.2 -R.sub.1, Met-R.sub.1 -L-R.sub.2, Met-R.sub.2 -L-R.sub.1, Met-R.sub.1 -R.sub.2, Met-R.sub.2 -R.sub.1, Ala-R.sub.1 -L-R.sub.2, Ala-R.sub.2 -L-R.sub.1, Ala-R.sub.1 -R.sub.2 and Ala-R.sub.2 -R.sub.1 ;
• wherein
• R.sub.1 is a human (15-125) interleukin-3 mutant polypeptide sequence of SEQ ID NO:8;
• Xaa at position 4 is Asn or Ile;
• Xaa at position 5 is Met, Ala or Ile;
• Xaa at position 6 is Ile, Pro or Leu;
• Xaa at position 9 is Ile, Ala or Leu;
• Xaa at position 11 is Thr or His;
• Xaa at position 15 is Gln, Arg, Val or Leu;
• Xaa at position 18 is Leu, Ala, Asn or Arg;
• Xaa at position 20 is Leu or Ser;
• Xaa at position 23 is Phe, Pro, or Ser;
• Xaa at position 24 is Asn or Ala;
• Xaa at position 28 is Gly, Ala, Ser, Asp or Asn;
• Xaa at position 31 is Gln, Val, or Met;
• Xaa at position 32 is Asp or Ser;
• Xaa at position 35 is Met, Ile, Leu or Asp;
• Xaa at position 36 is Glu or Asp;
• Xaa at position 37 is Asn, Arg or Ser;
• Xaa at position 41 is Arg, Leu, or Thr;
• Xaa at position 42 is Pro or Ser;
• Xaa at position 45 is Glu or Leu;
• Xaa at position 46 is Ala or Ser;
• Xaa at position 48 is Asn, Val or Pro;
• Xaa at position 49 is Arg or His;
• Xaa at position 51 is Val or Ser;
• Xaa at position 53 is Ser, Asn, His or Gly;
• Xaa at position 55 is Gln or Glu;
• Xaa at position 59 is Ala or Gly;
• Xaa at position 62 is Ser, Ala or Pro;
• Xaa at position 65 is Lys, Arg or Ser;
• Xaa at position 67 is Leu, Glu, or Val;
• Xaa at position 68 is Leu, Glu, Val or Trp;
• Xaa at position 71 is Leu or Val;
• Xaa at position 73 is Leu, Ser or Trp;
• Xaa at position 74 is Ala or Trp;
• Xaa at position 77 is Ala or Pro;
• Xaa at position 79 is Pro or Ser;
• Xaa at position 81 is His or Thr;
• Xaa at position 84 is His, Ile, or Thr;
• Xaa at position 86 is Lys or Arg;
• Xaa at position 87 is Asp;
• Xaa at position 91 is Asn or Gln;
• Xaa at position 95 is Arg, Glu, Leu;
• Xaa at position 98 is Thr or Gln;
• Xaa at position 102 is Lys;
• Xaa at position 103 is Thr or Ser;
• Xaa at position 106 is Asn, Gln, or His;
• and
• Xaa at position 109 is Ala or Glu;
• wherein from one to three of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein a polypeptide having only said human interleukin-3 mutant sequence has at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of:
• AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay;
• R.sub.2 is a factor selected from the group consisting of:
• a colony stimulating factor, a cytokine, a lymphokine, and interleukin, and a hematopoietic growth factor;
• and
• L is a linker capable of linking R.sub.1 to R.sub.2.