Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients.

摘要: Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major obstacle in the treatment patients with acute myeloid leukaemia (AML). Deficiency functional deoxycytidine kinase (dCK) plays an important role AraC vitro. We screened 5378 bp sequences dCK gene, including all exons and 5' flanking region, identified two single nucleotide polymorphisms (SNPs) regulatory region (rSNPs) high allele frequencies. These rSNPs (-201C>T -360C>G) formed haplotypes. Genotyping sequencing MassARRAY system among 122 AML showed that those -360CG/-201CT -360GG/-201TT compound genotypes (n = 41) displayed favourable response chemotherapy whereas -360CC/-201CC 81) tended have poor (P 0.025). Moreover, real-time quantitative reverse transcriptase-polymerase chain reaction expressed higher level mRNA compared genotype 0.0034). Luciferase-reporter assay bearing -360G/-201T alone had eight-fold greater transcriptional activation activity -360C/-201C genotype, co-transfection both constructs mimicked heterozygous which exhibited four-fold -360C/-201C. results indicate rSNP haplotypes gene may serve as genetic marker for predicting drug responsiveness, will be beneficial establishing more effective chemotherapeutic regimens.