Harju, T., Hurme-Niiranen, A., Suo-Palosaari, M. et al. DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?. Pharmacogenomics J 23, 105–111 (2023). https://doi.org/10.1038/s41397-023-00303-0
DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia : is there a causal relationship?
|Author:||Harju, Tekla1,2; Hurme-Niiranen, Anri1,3; Suo-Palosaari, Maria4,5;|
1Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
2Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
3Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
4Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
5Research Unit of Health Sciences and Technology, Oulu University Hospital and University of Oulu, Oulu, Finland
6Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, and Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
7Biocenter Oulu, University of Oulu, Oulu, Finland
8Pediatric Oncology Laboratory, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
9Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
|Online Access:||PDF Full Text (PDF, 0.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20231020140693
|Publish Date:|| 2023-10-20
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.
|Pages:||105 - 111|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3123 Gynaecology and paediatrics
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. Open Access funding provided by University of Oulu including Oulu University Hospital.
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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