Publication: Tpmt*3c as a predictor of 6-mercaptopurine-induced myelotoxicity in thai children with acute lymphoblastic leukemia
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Issued Date
2021
Resource Type
Language
eng
File Type
application/pdf
ISSN
20754426
Other identifier(s)
2-s2.0-85113156828
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Journal of Personalized Medicine. Vol 11, No.8 (2021)
Suggested Citation
Jantararoungtong T., Wiwattanakul S., Tiyasirichokchai R., Prommas S., Sukprasong R., Koomdee N., Jinda P., Rachanakul J., Nuntharadthanaphong N., Pakakasama S., Anurathapan U., Hongeng S., Sukasem C. Tpmt*3c as a predictor of 6-mercaptopurine-induced myelotoxicity in thai children with acute lymphoblastic leukemia. Journal of Personalized Medicine. Vol 11, No.8 (2021). doi:10.3390/jpm11080783 Retrieved from: https://hdl.handle.net/20.500.14740/5553
Abstract
The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes (TPMT 719A > G (*3C), ITPA 94C > A and ITPA 123G > A) and drug transporters (MRP4 912C > A and MRP4 2269G > A) with 6-MP-related myelotoxicity and hepatotoxicity in Thai children with acute lymphoblastic leukemia (ALL). The prescribed dosage of 6-MP and its adverse effects were assessed from medical records during the first 8 weeks and 9–24 weeks of maintenance therapy. Children with the TPMT*1/*3C genotype had a higher risk of leukopenia with an odds ratio (OR) of 4.10 (95% confidence interval (CI) of 1.06–15.94; p = 0.033) compared to wild type (TPMT*1/*1) patients. Heterozygous TPMT*3C was significantly associated with severe neutropenia with an increased risk (OR, 4.17; 95% CI, 1.25–13.90); p = 0.014) during the first 8 weeks. No association was found among ITPA 94C > A, ITPA 123G > A, MRP4 912C > A, and MRP4 2269G > A with myelotoxicity and hepatotoxicity. The evidence that TPMT heterozygotes confer risks of 6-MP-induced myelotoxicity also supports the convincing need to genotype this pharmacogenetic marker before the initiation of 6-MP therapy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subject(s)
ABC transporter subfamily B
Cyclophosphamide
Cytarabine
Drug metabolizing enzyme
Mercaptopurine
Methotrexate
Multidrug resistance associated protein 4
Prednisolone
Thiopurine methyltransferase
Vincristine
Acute lymphoblastic leukemia
Article
Blood sampling
Bone marrow toxicity
Child,human
Controlled study
Cytochemistry
Female
Gene frequency
Genetic association
Genetic polymorphism
Genetic variability
Genotype
Human
Immunophenotyping
Leukocyte count
Leukopenia
Liver toxicity
Maintenance therapy
Major clinical study
Male
Medical record
Neutropenia
Neutrophil count
Platelet count
Polymerase chain reaction
Preschool child
Single nucleotide polymorphism
Thai (people)
Thrombocytopenia
Cyclophosphamide
Cytarabine
Drug metabolizing enzyme
Mercaptopurine
Methotrexate
Multidrug resistance associated protein 4
Prednisolone
Thiopurine methyltransferase
Vincristine
Acute lymphoblastic leukemia
Article
Blood sampling
Bone marrow toxicity
Child,human
Controlled study
Cytochemistry
Female
Gene frequency
Genetic association
Genetic polymorphism
Genetic variability
Genotype
Human
Immunophenotyping
Leukocyte count
Leukopenia
Liver toxicity
Maintenance therapy
Major clinical study
Male
Medical record
Neutropenia
Neutrophil count
Platelet count
Polymerase chain reaction
Preschool child
Single nucleotide polymorphism
Thai (people)
Thrombocytopenia