BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate

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Laine Celestino Pinto
https://orcid.org/0000-0003-4246-5714
Lívia de Oliveira Sales
https://orcid.org/0000-0003-1214-5250
Tereza Cristina de Brito Azevedo
https://orcid.org/0000-0002-9352-326X
Caroline Aquino Moreira-Nunes
https://orcid.org/0000-0001-5845-3481
José Alexandre Rodrigues Lemos
https://orcid.org/0000-0002-7595-2597

Abstract

Objective: Chronic Myeloid Leukemia (CML) is a clonal disorder of hematopoietic progenitor cells, characterized by a reciprocal translocation between chromosomes 9 and 22, which results in the hybrid gene BCR-ABL1. Even with the progress in the treatment of the disease allowed by tyrosine kinase inhibitors, point mutations in this gene's domain are the main causes of therapeutic resistance, mainly to imatinib mesylate. This study aimed to analyze the point mutations of high resistance in a patient with CML and its possible correlation with treatment response. Methods: Cross-sectional study with 58 CML patients undergoing treatment with imatinib and with suboptimal response to therapy. Blood samples were analyzed by real-time PCR using TaqMan® chemistry to evaluate the following point mutations: T315I, E255V and Y253H. Results: None of the 58 patients had any of the investigated mutations. There was irregular use of the medication in 16% (n = 9), of which 44% (n = 4) reported discontinuous use and interruption on their own, and 56% (n = 5) showed intolerance to treatment and switched drugs. Conclusion: The absence of point mutations in CML patients analyzed in this study demonstrated that failure in therapy has no molecular correlation with the analyzed mutations and may be related to lower treatment adherence rates. These findings were demonstrated in a considerable number of evaluated patients, pointing out the need for education on the importance of following the recommendations on their treatment to avoid future complications.



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How to Cite
1.
Pinto LC, Sales L de O, Azevedo TC de B, Moreira-Nunes CA, Lemos JAR. BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate. HSJ [Internet]. 2020 Dec. 10 [cited 2024 Nov. 22];10(4):77-84. Available from: https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994
Section
ORIGINAL ARTICLE
Author Biographies

Laine Celestino Pinto, Experimental Laboratory of Neuropathology (Lanex), Federal University of Pará

PhD in Genetics and Molecular Biology. Federal University of Pará (UFPA). Belém, Pará, Brazil.

Lívia de Oliveira Sales, Laboratory of Pharmacogenetics, Nucleus for Research and Development of Medicines (NPDM), Federal University of Ceará

Post-Graduate student in Clinical Pharmacology at the Federal University of Ceará (UFC). Fortaleza, Ceará, Brazil.

Tereza Cristina de Brito Azevedo, Department of Clinical and Academic Research, Ophir Loyola Hospital.

Master in Genetics and Molecular Biology from the Federal University of Pará (UFPA). PhD student in the Postgraduate Program in Oncology and Medical Sciences at UFPA. Oncohematologist, Ophir Loyola Hospital. Belém, Pará, Brazil.

Caroline Aquino Moreira-Nunes, Laboratory of Pharmacogenetics, Nucleus for Medicines Research and Development (NPDM), Federal University of Ceará

Master and PhD in Genetics and Molecular Biology by the Federal University of Pará (UFPA). Postdoctoral with emphasis on Genetics of Hereditary Tumors and Postdoctoral in Pharmacology. Professor and advisor in the Postgraduate Courses in Clinical Pharmacology and Translational Medicine at the Federal University of Ceará (UFC). Researcher at the Nucleus for Medicines Research and Development of UFC, Fortaleza, Ceará, Brazil.

José Alexandre Rodrigues Lemos, Institute of Biological Sciences, Federal University of Pará

Master and PhD in Genetics from the University of São Paulo (USP). Full Professor at the Institute of Biological Sciences at the Federal University of Pará (UFPA). Belém, Pará, Brazil.

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