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KMID : 0387820080150010001
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Clinical Pediatric Hematology-Oncology
2008 Volume.15 No. 1 p.1 ~ p.9
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Genetic Polymorphism of Thiopurine Methyltransferase in Children with Acute Lymphoblastic Leukemia
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Cho Han-Gil
Baek Hee-Jo
Han Dong-Kyun
Bae Si-Young
Kook Hoon
Hwang Tai-Ju
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Abstract
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Purpose: 6-mercaptopurine (6-MP) is a very important drug in pediatric patients for the maintenance treatment of acute lymphoblastic leukemia (ALL). 6-MP is catabolized by thiopurine methyltransferase (TPMT). TPMT activity, one of the related factors for toxicity or efficacy of 6-MP, is determined by genetic polymorphisms. The aim of this study is to screen TPMT genetic polymorphism in Korean pediatric ALL.
Methods: The study included 44 children with ALL who were treated between May, 2007 and August, 2007 at Chonnam National University Hwasun Hospital. TPMT genotypes were analyzed by using polymerase chain reaction and gene sequencing from peripheral blood white blood cell.
Results: Most of the patients had homozygous wild type (43/44, 97.7%), while only one (2.3%) had heterozygous mutant type. The percentage of dose reduction of 6-MP during maintenance chemotherapy was not different between wild type TPMT*1/*1 (n=39) and TPMT*1/*3C variant (n=1). Thirty-three of 39 TPMT*1/*1 type experienced adverse effects such as hepatotoxicity (n=11; median frequency, 2.3) and hematopoietic toxicity (n=18; median frequency, 2.2). One TPMT*1/*3C variant experienced 2 episodes of hepatotoxicity and hematopoietic toxicity, respectively.
Conclusion: The TPMT*1/ *3C variant was detected in one patient among 44 cases with ALL. Many patients with wild type TPMT also could not tolerate planned 6-MP doses. A large study of TPMT polymorphism seems to be necessary to establish the standard 6-MP dosage by TPMT genotypes in Korea.
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KEYWORD
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Thiopurine methyltransferas, Polymorphism, Acute lymphoblastic leukemia, 6-mercaptopurine
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