Análise de mutações do domínio BCR-ABL quinase em pacientes com leucemia mielóide crônica refratários ao tratamento com mesilato de imatinibe
2020
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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