Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia.

Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia. Haematologica. 2020 Jul 16;: Authors: Martín-Izquierdo M, Abáigar M, Hernández-Sánchez JM, Tamborero D, López-Cadenas F, Ramos F, Lumbreras E, Madinaveitia-Ochoa A, Megido M, Labrador J, Sánchez-Real J, Olivier C, Dávila J, Aguilar C, Rodríguez JN, Martín-Nuñez G, Santos-Mínguez S, Miguel-García C, Benito R, Díez-Campelo M, Hernández-Rivas JM Abstract Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discovery cohort) and 14 paired samples from MDS patients who did not progress to sAML during follow-up (control cohort). Results were validated in an independent series of 388 MDS patients (validation cohort). We used an integrative analysis to identify how mutations, alone or in combination, contribute to leukemic transformation. The study showed that MDS progression to sAML is characterized by greater genomic instability and the presence of several types of mutational dynamics...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research