Admixture Mapping Reveals Candidate Regions for Methotrexate Neurotoxicity Susceptibility: A Reducing Disparities in Acute Leukemia Consortium Report
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Le résumé fourni par la source
BACKGROUND: Neurotoxicity is a rare, often dose-limiting adverse effect of methotrexate (MTX) therapy that disproportionally affects Latino children. Factors contributing to the observed disparity are not well understood. This study leveraged admixture mapping to identify genetic regions associated with MTX-related neurotoxicity susceptibility among Latino children undergoing therapy for pediatric acute lymphoblastic leukemia (ALL). PROCEDURE: The study cohort was composed of 429 self-identifying Latino children diagnosed with ALL (2005-2019) between the ages of 2 and 20 years treated at one of six US pediatric cancer treatment centers. MTX-related neurotoxicity was defined as neurologic episodes (e.g., seizures, stroke-like symptoms, altered mental status, and tremors) occurring within 21 days of intravenous (IV) and/or intrathecal (IT) MTX that were documented by magnetic resonance imaging (MRI) abnormalities and/or clinical symptoms. Among the 429 patients, we identified 46 (10.7%) Latino children with neurotoxicity. Admixture mapping was used to identify local genomic regions that are associated with the risk of MTX-related neurotoxicity among Latino children with ALL. CONCLUSIONS: Ultimately, this study identified 11 genomic regions carrying suggestive associations with MTX-neurotoxicity risk among Latino children with ALL. Review of biological plausibility of the loci within these regions revealed associations with areas of the brain or downstream regulatory functions. Results from this study may guide future work to further interrogate these regions through fine-mapping to identify genetic variants associated with increased risk of MTX-related neurotoxicity among Latino children with ALL.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Admixture Mapping Reveals Candidate Regions for Methotrexate Neurotoxicity Susceptibility: A Reducing Disparities in Acute Leukemia Consortium Report
- Date Crossref
- 03/08/2026
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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St. Jude Children's Research Hospital pays non établi dans la noticeÉtablissement de santé
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The University of Texas Health Science Center at Houston pays non établi dans la noticeUniversité ou école supérieure
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Department of Epidemiology Human Genetics and Environmental Sciences University of Texas Health Science Center at Houston Houston Texas USA pays non établi dans la noticeUniversité ou école supérieure
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Department of Public Health Peter O'Donnell School of Public Health University of Texas Southwestern Medical Center Dallas Texas USA pays non établi dans la noticeUniversité ou école supérieure
St. Jude Children's Research Hospital, The University of Texas Health Science Center at Houston et Baylor College of Medicine, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.