Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia
| Autor: | Ricardo Pasquini, Vaneuza Araujo Moreira Funke, Heloísa Zorzi Costa, Noemi F. Pereira, Ana Lucia Vieira Mion, Luciane kaminski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
medicine.drug_class
Resistance medicine.disease_cause Tyrosine-kinase inhibitor 03 medical and health sciences symbols.namesake 0302 clinical medicine hemic and lymphatic diseases Immunology and Allergy Medicine Sanger sequencing Tyrosine kinase inhibitors Mutation business.industry lcsh:RC633-647.5 Breakpoint Chronic myeloid leukemia breakpoint cluster region Myeloid leukemia Hematology lcsh:Diseases of the blood and blood-forming organs medicine.disease BCR-ABL1 gene Leukemia 030220 oncology & carcinogenesis Cancer research symbols Original Article business Tyrosine kinase 030215 immunology |
| Zdroj: | Hematology, Transfusion and Cell Therapy, Vol 40, Iss 4, Pp 363-367 (2018) Hematology, Transfusion and Cell Therapy Hematology, Transfusion and Cell Therapy, Volume: 40, Issue: 4, Pages: 363-367, Published: OCT 2018 |
| ISSN: | 2531-1379 |
| Popis: | Introduction: Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance. Objective: To evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná. Methods: This retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing. Results: Sixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53: 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I). Conclusions: This molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner. Keywords: Chronic myeloid leukemia, BCR-ABL1 gene, Mutation, Tyrosine kinase inhibitors, Resistance |
| Databáze: | OpenAIRE |
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