학술논문
Alterations in pharmacogenetic genes and their implications for imatinib resistance in Chronic Myeloid Leukemia patients from an admixed population.
Document Type
Academic Journal
Author
Cereja-Pantoja KBC; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; de Brito Azevedo TC; Ophir Loyola Hospital, Belém, PA, 66063-240, Brazil.; Vinagre LWMS; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; de Moraes FCA; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil. francisco.cezar2205@gmail.com.; da Costa Nunes GG; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Monte N; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; de Alcântara AL; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Cohen-Paes A; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Fernandes MR; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Batista Dos Santos SE; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; de Assumpção PP; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Ribeiro Dos Santos ÂK; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.; Burbano RMR; Ophir Loyola Hospital, Belém, PA, 66063-240, Brazil.; Guerrero RC; Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas - CiMUS, Universidad de Santiago de Compostela, Santiago de Compostela, 15782, Spain.; Carracedo Á; Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas - CiMUS, Universidad de Santiago de Compostela, Santiago de Compostela, 15782, Spain.; Carneiro Dos Santos NP; Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, PA, 66073-005, Brazil.
Source
Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0843 (Electronic) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE
Subject
Language
English
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.)
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)