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DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia : is there a causal relationship? |
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| Author: | Harju, Tekla1,2; Hurme-Niiranen, Anri1,3; Suo-Palosaari, Maria4,5; |
| Organizations: |
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 |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 0.8 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe20231020140693 |
| Language: | English |
| Published: |
Springer Nature,
2023
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| Publish Date: | 2023-10-20 |
| Description: |
AbstractHepatotoxicity 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. see all
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| Series: |
Pharmacogenomics journal |
| ISSN: | 1470-269X |
| ISSN-E: | 1473-1150 |
| ISSN-L: | 1470-269X |
| Volume: | 23 |
| Issue: | 5 |
| Pages: | 105 - 111 |
| DOI: | 10.1038/s41397-023-00303-0 |
| OADOI: | https://oadoi.org/10.1038/s41397-023-00303-0 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3123 Gynaecology and paediatrics |
| Subjects: | |
| Funding: |
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. |
| Dataset Reference: |
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. |
| Copyright information: |
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |