Avaliação da frequência das alterações citogenéticas e de expressão gênica em LMA ao diagnóstico e, sequencialmente, na remissão

• Ano de defesa: 2016
• Autor(a) principal: Serehi, Daniele Canavezi [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: genetic expression; citogenetics; acute myeloid leukemia; diagnosis; remission; expressão gênica; citogenética; leucemia mieloide aguda; diagnóstico; remissão
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4316087; https://repositorio.unifesp.br/handle/11600/46873

Acute myeloid leukemias (AML) are genetic heterogeneous neoplastic diseases. Distinctive clinical features in each subtype requires attention to define the proper disease classification and prognostic factors. With the recent reports of the increasing number of mutations and alternative pathways that regulates gene expression in AML, it becomes a challenge to establish an investigative conduct covering the widest possible range of the disease alterations, especially when there are a few studies assessing the scope of gene expression and cytogenetics in patients with AML.Therefore, a better understanding of genetic aspects of the disease is essential to propose improvements. Objective: Evaluate the frequency of different cytogenetic changes and the expression of some genes in adult patients with AML and correlate them with the clinical characteristics at diagnosis, the hematologic remission and risk stratification. Methods: We performed G-band karyotype of bone marrow aspirate; FISH-panel AML/MDS or PCR for PML-RARA, when there was no result of the karyotype, gene expressions analysis of FLT3, NPM1, CEBPA, WT1, RUNX1, MLL, CKIT, NRAS and KRAS via real-time PCR and mutation analysis of FLT3, NPM1 and CKIT genes. Results: In 55 cases, 80% of the karyotype, FISH and PCR to PML-RARA results were obtained, with a frequency of 53% rearrangements detected. In 44 patients it was possible to assess gene expression and analysis of mutations, with a frequency of 52% abnormal gene expressions - 32% in more than one gene, and 20.4% of mutations, indicating that gene expression can be influenced by other pathways, besides the mutations, to produce the leukemic cell phenotype. Conclusion: This study demonstrates the range of genetic alterations, many ongoing and unrelated to mutations, that can be found in patients with AML and offers a different view on the investigative approach of these diseases, endorsing the necessity for a broad diagnosis to trace an accurate profile of each case and properly determine the risk stratification and prognosis.