Influence of thymidylate synthase gene polymorphisms on high-dose methotrexaterelated toxicities in childhood acute lymphoblastic leukemia

Abstract:

Objective To investigate the influence of thymidylate synthase (TS) gene polymorphisms on highdose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL). Methods A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured. Results The main HDMTX- related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05). Conclusions TS gene polymorphisms have no influence on the incidence of HDMTX- related toxicities in childhood ALL.