Identificação de mutações que conferem resistência ao tratamento com inibidores de tirosina cinase
The chronic myeloid leukemia (CML) is characterized by a cytogenetic alteration known as Philadelphia chromosome (Ph), a result of reciprocal translocation t (9; 22) (q34; q11). The resulting fusion bcr-abl gene encodes a protein with tyrosine kinase constitutive activity that deregulates signal tra...
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| Format: | master thesis |
| Status: | Published version |
| Publication Date: | 2013 |
| Country: | Brasil |
| Institution: | Universidade Federal do Espírito Santo (UFES) |
| Repository: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
| Language: | Portuguese |
| OAI Identifier: | oai:repositorio.ufes.br:10/4464 |
| Online Access: | http://repositorio.ufes.br/handle/10/4464 |
| Access Level: | Open access |
| Keyword: | Chronic Myeloid Leukemia Tyrosine Kinase Inhibitors Mutation Leucemia Mielóide Crônica Inibidores de tirosina cinase Mutação Biotecnologia 61 |
| Summary: | The chronic myeloid leukemia (CML) is characterized by a cytogenetic alteration known as Philadelphia chromosome (Ph), a result of reciprocal translocation t (9; 22) (q34; q11). The resulting fusion bcr-abl gene encodes a protein with tyrosine kinase constitutive activity that deregulates signal transduction inducing proliferation, apoptosis, and cellular differentiation. The natural evolution of CML is currently changing with the development of tyrosine kinase inhibitors (TKI). Imatinib (Gleevec® , Novartis) was the first TKI approved for the treatment of CML. The eight-year update of the international randomized study of interferon and imatinib (IRIS), confirmed the efficacy and safety of imatinib in the long term with an overall survival of 85% and an event-free survival of 81%. However, some mutations in the kinase domain BCR-ABL confer resistance to one or more TKI, influencing the choice of therapy, as in the case of a T315I mutation, which is highly resistant to imatinib. Although many factors contribute to the resistance to imatinib, the presence of mutations is more prevalent and has been further investigated. Therefore, were aimed to perform mutation analysis in patients with a resistant phenotype of two cancer reference hospitals in Vitoria, ES, Brazil. We also developed a CML database relating clinical information and laboratory cytogenetics and molecular biology results, facilitating the monitoring of CML patients, as well as the understanding of disease progression. |
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