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

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 k...

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Detalles Bibliográficos
Autores: Pinto, Laine Celestino, Sales, Lívia de Oliveira, Azevedo, Tereza Cristina de Brito, Moreira-Nunes, Caroline Aquino, Lemos, José Alexandre Rodrigues
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Brasil
Institución:Hospital de Clínicas de Itajubá
Repositorio:Revista Ciências em Saúde
Idioma:portugués
OAI Identifier:oai:ojs.portalrcs.hcitajuba.org.br:article/994
Acceso en línea:https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994
Access Level:acceso abierto
Palabra clave:antineoplastics
bcr-abl proto-oncogenes
chronic myeloid leukemia
imatinib mesylate
therapeutic adherence
Chronic myeloid leukemia
adesão terapêutica
antineoplásicos
genes abl
leucemia mieloide crônica
mesilato de imatinibe
Leucemia mielóide crˆônica
Descripción
Sumario: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.