[Effect of MDR1 and CYP3A5 gene polymorphisms on outcomes of patients receiving imatinib treatment for chronic myeloid leukemia].

ABSTRACT: OBJECTIVE:To study the effect of MDR1 and CYP3A5 gene polymorphisms on the outcomes of imatinib treatment in patients with chronic myeloid leukemia (CML). METHODS:A total of 100 patients with CML treated with imatinib were enrolled in this study, including 50 patients with cytogenetic relapse (study group) and 50 without cytogenetic relapse (control group) during the follow-up for 45 months. For all the patients, single nucleotide polymorphisms (SNPs) of C1236T, C3435T, and G2677T/A loci in the MDR1 gene and A6986G locus in CYP3A5 gene were genotyped and the trough levels of imatinib was measured using LC-MS/MS. The relationship between SNPs of the loci and the risk of cytogenetic relapse were analyzed. RESULTS:The risk of cytogenetic recurrence was significantly higher in patients with CC genotypes of MDR1-C1236T and MDR1-C3435T than in those with CT + TT genotypes (P < 0.05). The median survival time of the patients with TT genotypes of MDR1-C3435T and MDR1-C1236T was significantly higher than that of patients with CC genotypes and CT genotypes (P < 0.05). The incidences of hematologic toxicity and neutropenia were significantly higher in patients with cytogenetic relapse than in those without cytogenetic relapse (P < 0.05). MDR1-C3435T genotype and imatinib concentration were independent predictors of cytogenetic relapse of CML. CONCLUSIONS:The risk of cytogenetic relapse of CML was significantly affected by SNPs of C1236T and C3435T loci of MDR1 gene and blood imatinib concentration. MDR1-C3435T genotype can be used as a potential biomarker for predicting cytogenetic relapse in CML patients.

SUBMITTER: He Y 

PROVIDER: S-EPMC6765618 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature