title: [The effect of the adverse events with thiopurine S-methyltransferase gene mutation on outcome of childhood acute lymphoblastic leukemia].
abstract: OBJECTIVE
  To investigate thiopurine S-methyltransferase (TPMT) activity and gene promoter polymorphism to probe its significance of individual chemotherapy in acute lymphoblastic leukemia (ALL) children.
  
  
  METHODS
  HPLC method was carried out to determine TPMT activity (n=100), which activity at newly diagnosed. At the same time determination of TPMT activity in healthy children (n=180), these children come from the health care clinic. Using online primer3 software design primers, PCR products were purified. To sequence TPMT gene of the patients with clinical events(n=30). According to the method to analysis of correlation between TPMT activity and toxicity.
  
  
  RESULTS
  The average TPMT activities were (31.72±10.31) nmol·g⁻¹Hb·h⁻¹ and (30.70±9.67) nmol·g⁻¹Hb·h⁻¹ in ALL and healthy groups respectively, without gender differences of TPMT activities (P=0.45) in both groups. The TPMT activity with clinical events in newly diagnosed ALL patients (n=30) was (24.07±11.43) nmol·g⁻¹Hb·h⁻¹. There are significant differences of TPMT activities between severe bone marrow suppression [(20.96±7.24) nmol·g⁻¹Hb·h⁻¹] and ALL patients with clinical events groups (P<0.05). The TPMT activity of (40.46±8.18) nmol·g⁻¹Hb·h⁻¹ in recurrence children was also significantly different (P<0.05). TPMT activity in severe liver toxicity group was not significantly different (P=0. 930). Of TPMT gene sequencing in ALL patients with clinical events, only 3 children were heterozygosity mutations of TPMT*3C, while others homozygous genotype. There were significant differences of TPMT activities between heterozygosity genotype [(11.99±1.32) nmol·g⁻¹Hb·h⁻¹] and homozygous genotype groups [(24.95±11.32) nmol·g⁻¹Hb·h⁻¹] (P<0.05). There were five kinds of variations at the vicinity of the promoter region of -100 of tandem repeats (VNTR) polymorphism（*V3/*V3、*V3/*V4、*V4/*V4、*V5/*V5、*V4/*V6）without significant differences of TPMT activities among five kinds (P=0.186).
  
  
  CONCLUSIONS
  TPMT activity was related to the gene polymorphism. TPMT activity determination had prognostic value and guided individualized treatment.
authors.affiliation: Depatment of Hematology, Affiliated Children's Hospital,Soochow University, Suzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Cao
authors.forename: Zhi-xiang
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Yi-huan
authors.initials: YH
authors.lastname: Chai
authors.forename: Shao-yan
authors.initials: SY
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen-li
authors.initials: WL
authors.lastname: Zhao
authors.forename: Hai-long
authors.initials: HL
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase