Gene polymorphisms of ABC transporters are associated with clinical outcomes in children with acute lymphoblastic leukemia

Abstract

IntroductionGenetic variability affects clinical outcome in pediatric acute lymphocytic leukemia (ALL) patients. Evaluating gene polymorphisms in ABC transporters could help identify relapse risk and predict outcome.Material and methodsThe SNaPshot SNP technique was used to analyze single-nucleotide polymorphisms (SNPs) in the multidrug transporter 1 (MDR1), multidrug resistance associated proteins (MRP1, MRP2) and breast cancer resistance protein (BCRP) genes of 82 pediatric ALL patients. The association between the SNPs with risk of all events and death as well as with survival was evaluated by the univariate Cox proportional hazard model.ResultsThe BCRP G34A SNP was the only SNP significantly associated with ALL. Risk factors included pre-treatment WBC counts and post-treatment peripheral and bone marrow leukemic cell counts. We found no association between MDR1 SNPs with these factors. The BCRP C421A C/A and C/C genotypes were significantly associated with low pre-treatment WBC counts while MRP2 G1249A G/G was significantly associated with low levels of post-treatment peripheral and bone marrow leukemic cells. A combination of C1236T, G1249A and/or G34A SNPs was significantly associated with lower EFS and OS.ConclusionsPolymorphisms associated with risk of ALL and clinical outcome may be potential biomarkers to predict clinical outcome and improve prognosis in childhood ALL.