Molecular technologies for improved risk classification and therapy for acute lymphoblastic leukemia in children and adults

A method for predicting therapeutic outcome in a leukemia patient comprising:

• (a) obtaining a biological sample from a patient;
• (b) determining in said sample the expression level of gene products for the following genes:
• MIDKINE (neurite growth-promoting factor 2);
• ARHGEF (rho guanine nucleotide exchange factor 4);
• FYB (FYN-binding protein;
• FYB);
• CHST10 (carbohydrate sulfotransferase 10);
• DREBIN 1;
• SMAD1;
• HABP4 (hyaluronan-binding protein);
• PHYN (phytanoyl-CoA hydroxylase;
• Refsum disease);
• IFI44L (interferon-induced protein 44-like) (C1orf29);
• Human cDNA FLJ30991 fis, clone HLUNG1000041;
• ITPR3 (inositol 1,4,5-triphosphate receptor, type 3);
• NMT2 (N-myristoyltransferase 2)′ OPAL1;
• C10orf26 (hypothetical protein FLJ20154);
• NPY (neuropeptide Y);
• JAG1 (jagged 1;
• Alagille syndrome);
• MONDOA (Mlx Interactor);
• EFN-B2 (ephrin-B2);
• CDK8 (cyclin-dependent kinase 8);
• LGALS1 (lectin, galactoside-binding, soluble, galectin 1);
• DOK1 (docking protein 1, 62 kD, downstream of tyrosine kinase 1);
• GSTθ1 (glutathione-S-transferase omega 1);
• CCL5 (chemokine ligand 5)/RANTES;
• PRG1 (proteoglycan 1);
• CD44;
• ATP2C1 (ATPase, Ca++ transporting, type 2C, member 1);
• and optionally, SPARC (secreted protein, acidic, cysteine-rich;
• osteonectin) to yield observed gene expression levels;
• and
• (c) comparing the observed gene expression levels for the gene products to a control gene expression level selected from the group consisting of:
• (i) the gene expression level for the gene products observed in a control sample;
• and
• (ii) a predetermined gene expression level for the gene products;
• wherein an observed expression levels that is higher or lower than the control gene expression levels is indicative of predicted remission.

A method for screening compounds useful for treating acute lymphoblastic leukemia comprising:

• (a) determining the expression level for at least three gene products selected from the group consisting of midkine (neurite growth-promoting factor 2), CHST 10 (carbohydrate sulfotransferase 1 or HNK1-sulfotransferase), PHYN (phytanoyl-CoA hydroxylase), IF144L (Interferon-induced protein 44-like, C1orf29), OPAL 1, CDK8 (cyclin-dependent kinase 8), DOK1 (docking protein 1-62 kD and downstream of tyrosine kinase 1) and ATP2C1 (ATPase-Ca++ transporting type 2C member 1) in a cell culture to yield observed gene expression levels prior to contact with a candidate compound;
• (b) contacting the cell culture with a candidate compound;
• (c) determining the expression level for the gene products in the cell culture to yield observed gene expression levels after contact with the candidate compound;
• and
• (d) comparing the observed gene expression levels before and after contact with the candidate compound wherein a change in the gene expression levels after contact with the compound is indicative of therapeutic utility for said compound.

A method for screening compounds useful for treating acute lymphoblastic leukemia comprising:

• (a) contacting an experimental cell culture with a candidate compound;
• (b) determining the expression level for at least three gene products selected from the group consisting of midkine (neurite growth-promoting factor 2), OPAL1, HNK-1 sulfotransferase, phytanoyl-CoA hydroxylase (Refsum disease), cyclin-dependent kinase 8, docking protein 1 (62 kD and downstream of tyrosine kinase 1), ATPase (Ca++ transporting type 2C member 1), and optionally SPARC (secreted protein, acidic, cysteine-rich, osteonectin) in the cell culture to yield experimental gene expression levels;
• and
• (b) comparing the experimental gene expression levels to the expression level of the gene products in a control cell culture, wherein a relative difference in the gene expression levels between the experimental and control cultures is indicative of therapeutic utility.

A method for predicting therapeutic outcome in a leukemia patient comprising:

• (a) obtaining a biological sample from a patient;
• (b) determining in said sample the expression level for at least three gene products selected from the group consisting of LGALS1/galectin, DOK1, GST1, CCL5/RANTES, PRG1, CD44, ATP2C1, SPARC to yield observed gene expression levels;
• and
• (c) comparing the observed gene expression levels for the gene products to a control gene expression level selected from the group consisting of:
• (i) the gene expression level for the gene products observed in a control sample;
• and
• (ii) a predetermined gene expression level for the gene products;
• wherein an observed expression levels that is higher or lower than the control gene expression levels is indicative of predicted therapeutic failure.