Perfil da express??o de microRNAS envolvidos na regula????o hematopoi??tica em ves??culas extracelulares de pacientes com mielofibrose

• Ano de defesa: 2017
• Autor(a) principal: Silva, J??rdan Barros da
• Orientador(a): Pereira, Rinaldo Wellerson
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Cat??lica de Bras??lia
• Programa de Pós-Graduação: Programa Strictu Sensu em Ci??ncias Gen??micas e Biotecnologia
• Departamento: Escola de Sa??de e Medicina
• País: Brasil
• Palavras-chave em Português: Estroma; Medula ??ssea; Comunica????o celular
• Área do conhecimento CNPq: GENETICA
• Resumo em Inglês: Myelofibrosis (MF) is a rare disease that has an annual incidence of 1 in every 100,000 inhabitants in world, with an average survival of 69 months after diagnosis. Patients with MF have a delicate prognosis and common findings are increased platelet and erythrocyte counts, extramedullary hematopoiesis, hepatomegaly and splenomegaly, and medullary fibrosis. In recent years, several mutations have been reported in the literature, such as JAK2V617F, CalR and MPL, however, the only commercialized therapy so far (Ruxolitinib) has no curative potential. Extracellular vesicles (EVs) comprise a group of vesicles with a size of approximately 30 to 1000 nm and can carry molecules such as lipids, proteins and RNAs inside them. Due to these characteristics, several recent studies have demonstrated a relationship between the EVs and several types of clonal diseases, where patients with malignancies presented high levels of EV in the serum. Among the RNAs found the interior of the EVs, miRNAs are differentially expressed, since it is known that the small molecules are involved in several cellular processes. The present study has as a characteristic the trace of an EV profiles in patients with Myelofibrosis accompanied at the Hematology and Hemotherapy Unit of the Federal District Base Hospital, as well as a differential expression of the microRNAs miR-29a-3p, miR-155 -5p and miR-223-3p and correlate with the clinical features of the disease. The data show that miR-29a and miR-155 are differentially expressed in MF patients, both of which are downregulated. The miR-223 did not present significant differences. Knowing that the low expression of miR29a is related to an aberrant self-renewal of hematopoietic progenitor cells, the data presented here indicate that the EV may contribute to the pathophysiology of the disease.
• Link de acesso: https://bdtd.ucb.br:8443/jspui/handle/tede/2269

Myelofibrosis (MF) is a rare disease that has an annual incidence of 1 in every 100,000 inhabitants in world, with an average survival of 69 months after diagnosis. Patients with MF have a delicate prognosis and common findings are increased platelet and erythrocyte counts, extramedullary hematopoiesis, hepatomegaly and splenomegaly, and medullary fibrosis. In recent years, several mutations have been reported in the literature, such as JAK2V617F, CalR and MPL, however, the only commercialized therapy so far (Ruxolitinib) has no curative potential. Extracellular vesicles (EVs) comprise a group of vesicles with a size of approximately 30 to 1000 nm and can carry molecules such as lipids, proteins and RNAs inside them. Due to these characteristics, several recent studies have demonstrated a relationship between the EVs and several types of clonal diseases, where patients with malignancies presented high levels of EV in the serum. Among the RNAs found the interior of the EVs, miRNAs are differentially expressed, since it is known that the small molecules are involved in several cellular processes. The present study has as a characteristic the trace of an EV profiles in patients with Myelofibrosis accompanied at the Hematology and Hemotherapy Unit of the Federal District Base Hospital, as well as a differential expression of the microRNAs miR-29a-3p, miR-155 -5p and miR-223-3p and correlate with the clinical features of the disease. The data show that miR-29a and miR-155 are differentially expressed in MF patients, both of which are downregulated. The miR-223 did not present significant differences. Knowing that the low expression of miR29a is related to an aberrant self-renewal of hematopoietic progenitor cells, the data presented here indicate that the EV may contribute to the pathophysiology of the disease.