Mutações nos genes ASXL1, NRAS/KRAS, TP53 em pacientes com síndrome mielodisplásica e leucemia mielóide aguda secundária à síndrome mielodisplásica

• Autor(a) principal: Leite, Carolina de Andrade
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/8802
• topic: Myelodysplastic syndrome; Mutation; ASXL1; NRAS/KRAS; TP53; Síndrome mielodisplásica; Mutação; ASXL1; NRAS/KRAS; TP53; Mutação (Biologia); Síndromes mielodisplásicas; Genética Expressão; Idosos; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::HEMATOLOGIA

RESUMO Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis, apoptosis and increased risk of progression to acute myeloid leukemia (AML). Over the years, little has evolved regarding the handling of this entity. With the development of prognostic indicators such as IPSS (International Prognostic Scoring System) in 1997, WPSS (World Health Organization Prognostic Scoring System) in 2005 and, more recently, the IPSS-R (Revised International Prognostic Scoring System) in 2012, there was an improvement in the stratification and estimation of prognosis. IPSS is still considered the best option for MDS classification, but we often observe patients with different clinical behaviors coexisting in the same stratification group. It suggests that the currently available scores are imperfect and that there´s an urgent need for a more refined categorization. With the improvement in MDS studies, many researches have highlighted the importance of somatic mutations profiling as accountable factors for poor prognosis and disease progression. We studied 50 patients with MDS followed at the Pedro Ernesto University Hospital Hematology Service (HUPE) from 2012 to 2014. We analyzed mutations in ASXL1, NRAS/KRAS and TP53 genes, by extracting genomic DNA sequencing. Of the 50 patients studied, 42 (84%) had at least one kind of mutation. Mutation in gene ASXL1 was the most frequent in 41 patients (82%), followed by TP53 in 10 patients (20%) and NRAS in only one patient (2%). In LMA-t group, 11% had mutations in TP53 and 78% in ASXL1, and no mutation was found in NRAS or KRAS genes. This study showed no differences between the mutated and non-mutated groups with respect to overall survival, bone marrow fibrosis, need for transfusion or cytopenias. We expect to have more significant variations in this group in a long-term monitoring becomes available.