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dc.contributor.authorSantos, Marlúcia Oliveira dos-
dc.date.available2024-09-11-
dc.date.available2024-09-13T15:24:14Z-
dc.date.issued2024-05-02-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/5922-
dc.description.abstractAcute myeloid leukemia (AML) is a disease heterogeneous hematological, which develops in the bone marrow after genetic and epigenetic changes in hematopoietic precursors, resulting in the clonal proliferation of blast cells of the myeloid lineage. Variations in the FMS-Like Tyrosine kinase 3 (FLT3) gene, as internal tandem duplication (FLT3-ITD) and variant in the D835 codon are reported frequently 30% and 10% of the cases, respectively. These mutations are associated with poor survival and risk of relapse. However, data on other variants in the FLT3 exome are not reported. Objective: This study aimed to evaluate variants in FLT3 in patients with AML treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Methodology: Were evaluated 36 patients diagnosed with AML of both genders and aged between 18-92. Bone marrow samples were collected and identification of FLT3 exome variants was performed by Sanger sequencing. Results: Different FLT3 gene variants were identified, total of 26 variants in 18 patients. Missense variants were found in functional domains, as 6 (23.1%) extracellular (EC), 3 (11.5%) transmembrane (TM), 1 (3.9%) juxtamembrane (JM), 5 (19.2%) in the tyrosine kinase I domain (TKD1) and 4 (15.4%) tyrosine kinase II domain (TKD2). FLT3-ITD variants were identified 3 (11.5%) in the JM domain and 4 in TKD1 (15.4%). The allele frequency (VAF) of pathogenic variants ranged from 11-62.5%. Missense variants were related with intense thrombocytopenia (p=0.038) and increased blasts in peripheral blood (p=0.014). Higher hemoglobin values were observed in patients with FLT3-ITD (p=0.049). The presence of a variant in the FLT3 gene can be identified in patients with secondary AML and in relapse, as discussed in a report of 4 cases, therefore the majority were identified in new AML (75%). Conclusion: This study highlights the occurrence of different potentially pathogenic variants in the FLT3 gene in patients with AML, the missense variants as most prevalent and related with hematological changes, highlighting the importance of screening variants in the FLT3 exomept_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectLeucemia mieloide agudapt_BR
dc.subjectFLT3pt_BR
dc.subjectDuplicação interna em tandempt_BR
dc.subjectInibidores de FLT3pt_BR
dc.subjectVariante missensept_BR
dc.subjectAcute myeloid leukemiapt_BR
dc.titleAvaliação de variantes do FLT3 em pacientes com leucemia mieloide aguda atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonaspt_BR
dc.title.alternativeEvaluation of FLT3 variants in patients with acute myeloid leukemia treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonaspt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2024-09-13T15:24:14Z-
dc.contributor.advisor-co1Passos, Leny Nascimento da Motta-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/8194622149198642pt_BR
dc.contributor.advisor1Silva, George Allan Villarouco da-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/1939667501234091pt_BR
dc.contributor.referee1Silva, George Allan Villarouco da-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/1939667501234091pt_BR
dc.contributor.referee2Costa, Allyson Guimarães da-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/7531662673281014pt_BR
dc.contributor.referee3Silva, Celso Arrais Rodrigues da-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/6962573800002763pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/6585900986900272pt_BR
dc.description.resumoA Leucemia Mieloide Aguda (LMA) é uma doença hematológica, heterogênea, que se desenvolve na medula óssea a partir de alterações genéticas e epigenéticas nos precursores hematopoiético, resultando na proliferação clonal de células blásticas da linhagem mieloide. Alterações no gene FMS- Like Tirosina quinase 3 (FLT3), como duplicação interna em tandem (FLT3-ITD) e variante no códon D835 são relatadas com frequência de 30% e 10% dos casos, respectivamente. Essas variantes são relacionadas a baixa sobrevida e risco de recaída. Entretanto, dados sobre outras alterações no gene FLT3 são pouco relatadas. Objetivo: Este estudo teve como objetivo avaliar variantes no FLT3 em pacientes com LMA atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Metodologia: Foram avaliados 36 pacientes com diagnóstico de LMA de ambos os gêneros com idade entre 18-92 anos. Amostras de medula óssea foram coletadas e a identificação de alterações no gene FLT3 foi realizada pelo sequenciamento de Sanger. Resultados: Diferentes variantes do gene FLT3 foram identificadas, total de 26 variantes em 18 pacientes. Variantes tipo missense foram encontradas nos domínios funcionais, como 6 (23,1%) extracelular (EC), 3 (11,5%) transmembranar (TM), 1 (3,9%) justamembranar (JM), 5 (19,2%) no domínio tirosina quinase I (TKD1) e 4 (15,4%) domínio tirosina quinase II (TKD2). FLT3-ITD foram identificadas 3 (11,5%) no domínio JM e 4 no TKD1 (15,4%). As variantes classificadas como patogênicas foram 19 (73,1%) com frequência alélica das variantes (VAF) de 11-62,5%. Variantes tipo missense foram relacionadas com intensa plaquetopenia (p=0,038) e aumento de blastos no sangue periférico (p=0,014). Maiores concentrações de hemoglobina foram observadas em pacientes com FLT3-ITD (p=0,049). A presença de variante no gene FLT3 pode ser identificada em paciente com LMA secundária e na recaída, como abordado em relato de 4 casos, portanto a maioria foram identificados em LMA novo (75%). Conclusão: Este estudo destaca a ocorrência de diferentes variantes patogênica no gene FLT3 em pacientes com LMA, as variantes missense como mais prevalentes e estão relacionadas com alterações hematológicas, destacando a importância do rastreio de variantes no gene FLT3pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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