Caracterización de las alteraciones genéticas de riesgo alto en los síndromes mielodisplásicosla transformación leucémica

Abstract

Myelodysplastic syndromes (MDS) constitute a large and heterogeneous group of chronic hematopoietic disorders that present a tumor phenotype characterized by clonality and dysplasia of the myeloid, erythroid and megakaryocytic lineages. This leads to ineffective hematopoiesis causing bone marrow hypercellularity and peripheral blood cytopenia.Around 30-40% of MDS progress to acute myeloid leukemia due to the acquisition of different mutations and selection of clones. The IPSS-R classifies MDS into five risk groups ( very low, low, intermediate, high and very high).Approximately 80% of patients with MDS have DNA alterations. More than 40 recurrently mutated genes have been described in this pathology. Some of the most frequent mutations occur in genes encoding transcription factors (TP53, RUNX1, ETV6), epigenetic regulators (TET2, DNMT3A, ASXL1, EZH2, IDH1 / 2), splicing factors or mRNA processors (SF3B1, SRSF2, U2AF1, ZRSR2) and cell signaling proteins (NRAS, CBL, JAK2, SETBP1). Several alterations have been described as molecular markers with independent prognostic value for this disease. However, the reason why some myelodysplastic syndromes show a greater tendency to leukemic transformation is still unknown despite not presenting complex karyotypes or mutations with a poor prognosis...