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dc.contributor.authorAquino, Deborah Canté de-
dc.date.available2024-02-05-
dc.date.available2024-02-07T14:53:47Z-
dc.date.issued2023-08-31-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/5522-
dc.description.abstractEssential thrombocythemia and myelofibrosis are chronic BCR::ABL1 negative myeloproliferative neoplasms characterized by exacerbated megakaryocyte proliferation and reactive deposition of fibrous connective tissue due to granulocyte and megakaryocyte hyperplasia, respectively. There are genetic variants in the coding sequence of the MPL gene (1p34.2) in both hematologic malignancies, identified in 3% of patients with essential thrombocythemia and 8% with myelofibrosis, which compromise the thrombopoietin receptor activity, making it hypersensitive and capable of dimerization independently of ligand interaction to activate the JAK-STAT signaling pathway, stimulating cell proliferation constitutively, leading to the phenotype of essential thrombocythemia and/or myelofibrosis. Objective: To identify genetic variants present in exon 10 of the MPL gene in patients with essential thrombocythemia and myelofibrosis treated at the HEMOAM Foundation. Methodology: The study was descriptive and cross-sectional, with the study population consisting of patients clinically diagnosed with the aforementioned neoplasms, of both sexes, aged 18 years and older, recruited between August 2021 and July 2022. Peripheral blood was collected for genomic DNA extraction from granulocytes. Molecular analysis was performed through Sanger sequencing, with electropherogram analysis conducted in Geneious software, and statistical analysis in Graphpad Prism for demographic and hematological data analysis. Results: 64 patients diagnosed with essential thrombocythemia and myelofibrosis were included. 85.27% of individuals corresponded to the essential thrombocythemia group, and 14.73% to the myelofibrosis group. The median age ranged from the sixth to the seventh decade of life in both groups. There was a higher predominance of women in essential thrombocythemia (78.95%), while myelofibrosis showed a balance between genders. Patients with myelofibrosis presented a higher frequency of splenomegaly (57.14%) compared to essential thrombocythemia (18.18%). Regarding hematological parameters, the myelofibrosis group showed lactate dehydrogenase levels above the reference range, while essential thrombocythemia demonstrated a significant increase in platelet count. In the molecular analysis, no genetic variants in exon 10 of the MPL gene were identified in the study population. Conclusion: The absence of variants in exon 10 of the MPL gene was observed. Further studies should be conducted with a larger population, considering the low frequency of variants in this gene in patients with essential thrombocythemia and myelofibrosispt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectW515Lpt_BR
dc.subjectW515Kpt_BR
dc.subjectReceptor de trombopoietinapt_BR
dc.subjectNeplasias mieloproliferativapt_BR
dc.subjectMyeloproliferative Neplasmspt_BR
dc.titleEstudo molecular do éxon 10 do gene MPL em pacientes com Trobocitemia essencial e mielofibrosept_BR
dc.title.alternativeMolecular study of exon 10 of the MPL gene in patients with Essential Throbocythemia and Myelofibrosispt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2024-02-07T14:53:47Z-
dc.contributor.advisor-co1Tarragô, Andréa Monteiro-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/4644326589690231pt_BR
dc.contributor.advisor1Mourão, Lucivana Prata de Souza-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.referee1Mourão, Lucivana Prata de Souza-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.referee2Almeida, Maria Edilene Martins de-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/9637683978812335pt_BR
dc.contributor.referee3Santos, Maria da Conceição Freitas dos-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/7618353060771291pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/2902751845968033pt_BR
dc.description.resumoTrombocitemia essencial e mielofibrose são neoplasias mieloproliferativas crônicas BCR::ABL1 negativas caracterizadas por hiperplasia exacerbada de megacariócitos e deposição reativa de tecido conjuntivo fibroso devido a hiperplasia de granulócitos e megacariócitos, respectivamente. Há a presença de variantes genéticas na sequência codificante do gene MPL (1p34.2) em ambas as malignidades hematológicas, identificadas em 3% dos pacientes com TE e 8% com MF, as quais comprometem a atividade do receptor de trombopoietina, tornando-o hipersensível e com dimerização independe da interação com o ligante para ativar a sinalização da via JAK-STAT, estimulando de forma constitutiva a proliferação celular, levando ao fenótipo de TE e/ou MF. Objetivo: identificar variantes genéticas presentes no éxon 10 do gene MPL em pacientes com trombocitemia essencial e mielofibrose atendidos da Fundação HEMOAM. Metodologia: estudo foi do tipo descritivo-transversal, teve como população de estudo os pacientes com diagnóstico clínico para as neoplasias supracitadas, ambos os sexos, a partir de 18 anos, recrutados entre agosto de 2021 a julho de 2022. Foi feita coleta de sangue periférico para extração de DNA de genômico de granulócitos. A análise molecular foi realizada por meio sequenciamento de Sanger, com análise de eletroferogramas realizada no software Geneious e análise estatística no Graphpad Prism para realização das análises de dados demográficos e hematológicos. Resultados: 64 pacientes diagnosticados com trombocitemia essencial e mielofibrose foram incluídos. 85,27% dos indivíduos correspondem ao grupo com TE e 14,73% na população com MF. A mediana de idade ficou entre a sexta e a sétima década de vida em ambos os grupos. Houve maior predominância de mulheres em trombocitemia essencial (78,95%), ao passo que em MF houve um equilíbrio entre os gêneros. Pacientes com mielofibrose apresentaram maior frequência de esplenomegalia (57,14%) em comparação a trombocitemia essencial (18,18%). No que tangem aos parâmetros hematológicos, o grupo mielofibrose apresentou índices de desidrogenase lática acima dos níveis de referência, ao passo que trombocitemia essencial demonstrou aumento significativo na contagem de plaquetas. Na análise molecular, não foram identificadas variantes genéticas no éxon 10 do gene MPL na população de estudo. Conclusão: verificou-se a ausência de variantes no éxon 10 do gene MPL. Estudos posteriores devem ser realizados com uma população maior, tendo em vista a baixa frequência de variantes nesse gene em pacientes com trombocitemia essencial e mielofibrosept_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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