title: [Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate-related toxicities in childhood acute lymphoblastic leukemia].
abstract: OBJECTIVE
  To investigate the influence of thymidylate synthase (TS) gene polymorphisms on high-dose 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 HD-MTX-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 HD-MTX-related toxicities in childhood ALL.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Hunan Normal University/Hunan Province People's Hospital, Changsha 410005, China. hexiangl021@163.com.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: He
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Wu
authors.forename: Run-Ying
authors.initials: RY
authors.lastname: Zou
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: You
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D008727:Methotrexate