DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?

Autor: Harju T; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland. tekla.harju@oulu.fi.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland. tekla.harju@oulu.fi., Hurme-Niiranen A; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.; Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland., Suo-Palosaari M; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.; Research Unit of Health Sciences and Technology, Oulu University Hospital and University of Oulu, Oulu, Finland., Nygaard Nielsen S; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, and Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Hinttala R; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.; Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland., Schmiegelow K; Pediatric Oncology Laboratory, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Uusimaa J; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.; Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland., Harila A; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden., Niinimäki R; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2023 Sep; Vol. 23 (5), pp. 105-111. Date of Electronic Publication: 2023 May 03.
DOI: 10.1038/s41397-023-00303-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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