DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?
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Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients. [Figure not available: see fulltext.]
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Pharmacogenomics Journal |
| Vol/bind | 23 |
| Udgave nummer | 5 |
| Sider (fra-til) | 105-111 |
| Antal sider | 7 |
| ISSN | 1470-269X |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank Laura Kytövuori, Ph.D. (Research Unit of Clinical Medicine, University of Oulu, Finland), Pirjo Keränen, and Anja Heikkinen for their help in the laboratory; Kirsi Kvist-Mäkelä (NordLab Oulu, Oulu University Hospital, Finland) for preparing patient samples; and Biocenter Oulu Sequencing Center (Finland) for their services. This work was supported by the Foundation for Pediatric Research; Special State Grants for Health Research in the Department of Pediatrics and Adolescence, Oulu University Hospital, Finland; the Alma and K.A. Snellman Foundation, Oulu, Finland; the Väre Foundation for Pediatric Cancer Research; the Finnish Medical Foundation; the Oulu University Grant Fund, Finland; Medical Research Center Oulu’s doctoral program, Oulu University Hospital and the University of Oulu, Finland; and the Danish Childhood Cancer Foundation, Denmark. The funders had no role in the study design, data collection, analysis, the decision to publish, or the preparation of the paper.
Funding Information:
We thank Laura Kytövuori, Ph.D. (Research Unit of Clinical Medicine, University of Oulu, Finland), Pirjo Keränen, and Anja Heikkinen for their help in the laboratory; Kirsi Kvist-Mäkelä (NordLab Oulu, Oulu University Hospital, Finland) for preparing patient samples; and Biocenter Oulu Sequencing Center (Finland) for their services. This work was supported by the Foundation for Pediatric Research; Special State Grants for Health Research in the Department of Pediatrics and Adolescence, Oulu University Hospital, Finland; the Alma and K.A. Snellman Foundation, Oulu, Finland; the Väre Foundation for Pediatric Cancer Research; the Finnish Medical Foundation; the Oulu University Grant Fund, Finland; Medical Research Center Oulu’s doctoral program, Oulu University Hospital and the University of Oulu, Finland; and the Danish Childhood Cancer Foundation, Denmark. The funders had no role in the study design, data collection, analysis, the decision to publish, or the preparation of the paper.
Publisher Copyright:
© 2023, The Author(s).
ID: 369078851