Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemia.

ABSTRACT: Methotrexate polyglutamates (MTXPGs) determine in vivo efficacy in acute lymphoblastic leukemia (ALL). MTXPG accumulation differs by leukemic subtypes, but genomic determinants of MTXPG variation in ALL remain unclear. We analyzed 3 types of whole genome variation: leukemia cell gene expression and somatic copy number variation, and inherited single nucleotide polymorphism (SNP) genotypes and determined their association with MTXPGs in leukemia cells. Seven genes (FHOD3, IMPA2, ME2, RASSF4, SLC39A6, SMAD2, and SMAD4) displayed all 3 types of genomic variation associated with MTXPGs (P < .05 for gene expression, P < .01 for copy number variation and SNPs): 6 on chromosome 18 and 1 on chromosome 10. Increased chromosome 18 (P = .002) or 10 (P = .036) copy number was associated with MTXPGs ev

SUBMITTER: French D 

PROVIDER: S-EPMC2680361 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature