Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients.

Autor: Ramalingam R; Department of Human Genetics, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Kaur H; Department of Human Genetics, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Scott JX; Department of Pediatric Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Sneha LM; Department of Pediatric Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Arunkumar G; MedGenome Labs Ltd., Bangalore, India., Srinivasan A; Department of Pediatric Oncology, Kanchi Kamakoti Child Trust Hospital, Chennai, Tamil Nadu, India., Paul SFD; Department of Human Genetics, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. paul@sriramachandra.edu.in.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2022 Mar; Vol. 89 (3), pp. 393-400. Date of Electronic Publication: 2022 Feb 14.
DOI: 10.1007/s00280-022-04405-7
Abstrakt: Purpose: Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs.
Methods: A total of 115 patients between the age of 1 and 18 years (average: 6.6) under maintenance therapy were selected for the study. SLC19A1 (c.80G > A), MTHFR (c.677C > T; c.1298A > C), and TYMS (c.*450_*455del) genotypes were determined using PCR techniques and Sanger sequencing. Cytogenetic and SNP findings were analyzed for any association with the reported toxicities using odds ratio, chi-square test, multifactor dimensionality reduction (MDR) analysis for synergistic effect and, multinomial logistic regression analysis for the likelihood of adverse events.
Results: Among the evaluated genetic variations, SLC19A1 (c.80G > A) was significantly associated with TRAEs (OR = 5.71, p = 0.002). Multinomial logistic regression analysis (chi-sq = 16.64, p < 0.001) and MDR analysis (chi-sq = 10.51 p < 0.001) confirmed the finding. On the other hand, no significant association was observed between adverse events and any specific cytogenetic aberration.
Conclusion: SLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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