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J Pediatr Genet 2021; 10(01): 029-034
DOI: 10.1055/s-0040-1715818
Original Article

Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients

Kanyarat Khaeso
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Nontaya Nakkam
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Patcharee Komwilaisak
2   Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Piyathida Wongmast
2   Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Su-on Chainansamit
3   Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand
,
Areerat Dornsena
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Sirimas Kanjanawart
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Suda Vannaprasaht
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
,
Wichittra Tassaneeyakul
1   Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
› Author Affiliations Funding This work was supported by grants from the Thailand Center of Excellence for Life Sciences (grant number TC-12/63) and the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (grant number 630000050064). Scholarship support from Graduate School, Khon Kaen University through the Research Fund for Supporting Lecturer to Admit High Potential Student to Study and Research on His Expert Program Year 2019 (grant number 621H219).
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Abstract

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2, NUDT15*5, and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.

Keywords

thiopurine methyltransferase - nucleoside diphosphate-linked moiety X-type motif 15 - pediatric acute lymphoblastic leukemia


Publication History

Received: 20 April 2020

Accepted: 10 June 2020

Article published online:
08 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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