Estudo molecular do éxon 10 do gene MPL em pacientes com Trobocitemia essencial e mielofibrose

Abstract

Essential 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 myelofibrosis