1. Alterations in pharmacogenetic genes and their implications for imatinib resistance in Chronic Myeloid Leukemia patients from an admixed population.
- Author
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Cereja-Pantoja KBC, de Brito Azevedo TC, Vinagre LWMS, de Moraes FCA, da Costa Nunes GG, Monte N, de Alcântara AL, Cohen-Paes A, Fernandes MR, Batista Dos Santos SE, de Assumpção PP, Ribeiro Dos Santos ÂK, Burbano RMR, Guerrero RC, Carracedo Á, and Carneiro Dos Santos NP
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Pharmacogenetics, Genotype, Young Adult, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Drug Resistance, Neoplasm genetics, Protein Kinase Inhibitors therapeutic use, Antineoplastic Agents therapeutic use, Polymorphism, Single Nucleotide
- Abstract
Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We investigated 129 patients diagnosed with Chronic Myeloid Leukemia treated with imatinib as first choice therapy. The participants of the study are highly admixed, populations that exhibit genetic diversity and complexity due to the contributions of multiple ancestral groups. Thus, the aim of this work was to investigate the association of 30 SNVs in genes related to response to treatment with Imatinibe in CML. Our results indicated that for the rs2290573 of the ULK3 gene, patients with the recessive AA genotype are three times more likely to develop resistance over time (secondary resistance) (p = 0.019, OR = 3.19, IC 95%= 1.21-8.36). Finally, we performed interaction analysis between the investigated variants and found several associations between SNVs and secondary resistance. We concluded that the variant rs2290573 of the ULK3 gene may be relevant for predicting treatment response of CML with imatinib, as well as possible treatment resistance. The use of predictive biomarkers is an important tool for therapeutic choice of patients, improving their quality of life and treatment efficacy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
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