Method for selective engraftment of drug-resistant hematopoietic stem cells

A method in which transgenic hematopoietic stem cells having a selective advantage over nontransgenic hematopoietic cells for engraftment are maintained in the mammal in the absence of selection, comprising:

• (a) administering a series of doses of a composition comprising an anti-folate, a vinca alkaloid, or an anthracycline to a mammal transplanted with a population of hematopoietic cells, at least a portion of which comprises a transgenic hematopoietic stem cell and a nontransgenic hematopoietic stem cell, wherein the genome of the transgenic hematopoietic cell has been augmented in vitro by a recombinant DNA comprising a promoter functional in hematopoietic stem cells operably linked to a first preselected DNA segment which encodes resistance or tolerance to the anti-folate, vinca alkaloid, or anthracycline, wherein the expression of the recombinant DNA in the transgenic hematopoietic stem cell in the mammal and the administration of the series of doses to the mammal results in a mammal in which the transgenic hematopoietic stem cell has a selective advantage in bone marrow engraftment relative to the nontransgenic hematopoietic cell;
• and
• (b) identifying a mammal from (a) in which a transgenic hematopoietic stem cell has engrafted and which mammal comprises progeny of the transgenic hematopoietic stem cell which are maintained in the mammal in the absence of the administration of the anti-folate, vinca alkaloid, or anthracycline.