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

Journal of Pediatric Genetics, Table of Contents

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

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Nontaya Nakkam

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Patcharee Komwilaisak

²Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Piyathida Wongmast

²Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Su-on Chainansamit

³Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand

,

Areerat Dornsena

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Sirimas Kanjanawart

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Suda Vannaprasaht

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

,

Wichittra Tassaneeyakul

¹Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

› Author Affiliations

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

Full Text

References

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