title: [Correlations between 6-mercaptopurine treatment-related adverse reactions in children with acute lymphoblastic leukemia and polymorphisms of thiopurine methyltransferase gene].
abstract: OBJECTIVE
  To explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities.
  
  
  METHODS
  Total RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed.
  
  
  RESULTS
  During the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05).
  
  
  CONCLUSIONS
  TPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.
authors.affiliation: Institute of Pediatric Research, Shenzhen Children's Hospital of Zunyi Medical College, Shenzhen, Guangdong 518026, China. 2376028869@qq.com.
authors.forename: Cai
authors.initials: C
authors.lastname: Xie
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Yue
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Ren
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Yang
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Zheng
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics
chemical_list: D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase