title: Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study.
abstract: BACKGROUND
  6-mercaptopurine (6-MP) is an essential component of pediatric acute lymphoblastic leukemia (ALL) maintenance therapy. Individual variability in this drug-related toxicity could be attributed in part to genetic polymorphism thiopurine methyltransferase (TPMT).
  
  
  OBJECTIVE
  To investigate the frequency of common TPMT polymorphisms in a cohort of Egyptian children with ALL and the possible relation between these polymorphisms and 6-MP with short-term complications.
  
  
  METHODS
  This study included 25 children. Data related to 6-MP toxicity during the maintenance phase were collected from the patients' files. DNA was isolated and genotyping for TPMT G460A, and A719G mutations were performed by polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  Twenty (80%) of the included 25 patients had a polymorphic TPMT allele. TPMT*3A was the most frequent (14/25, 56%), 8 patients were homozygous and 6 were heterozygous. TPMT*3C mutant allele was found in 4 patients (16%) in the heterozygous state while 2 patients (8%) were found to be heterozygous for TPMT*3B mutant allele. TPMT mutant patients, especially homozygous, were at greater risk of 6-MP hematological toxicity without significant difference regarding hepatic toxicity.
  
  
  CONCLUSIONS
  TPMT polymorphism was common among the studied group and was associated with increased risk of drug toxicity. A population-based multi-center study is required to confirm our results.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt.
authors.forename: Farida H
authors.initials: FH
authors.lastname: El-Rashedy
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt.
authors.forename: Seham Mohammed
authors.initials: SM
authors.lastname: Ragab
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Dawood
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt.
authors.forename: Shaymaa A
authors.initials: SA
authors.lastname: Temraz
keywords: 6-mercaptopurine; acute lymphoblastic leukemia; pharmacogenetic; polymorphism; thiopurine methyltransferase
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