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

Kanyarat Khaeso; Nontaya Nakkam; Patcharee Komwilaisak; Piyathida Wongmast; Su-On Chainansamit; Areerat Dornsena; Sirimas Kanjanawart; Suda Vannaprasaht; Wichittra Tassaneeyakul

doi:10.1055/s-0040-1715818

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

J Pediatr Genet. 2021 Mar;10(1):29-34. doi: 10.1055/s-0040-1715818. Epub 2020 Sep 8.

Authors

Kanyarat Khaeso¹, Nontaya Nakkam¹, Patcharee Komwilaisak², Piyathida Wongmast², Su-On Chainansamit³, Areerat Dornsena¹, Sirimas Kanjanawart¹, Suda Vannaprasaht¹, Wichittra Tassaneeyakul¹

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
² Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
³ Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand.

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

Grants and funding

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).