Molecular Pathogenesis and Treatment of Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are clonal hematological disorders arising from hematopoietic stem cells that have accumulated various genetic abnormalities. MDS are heterogeneous in nature but uniformly characterized by chronic and progressive cytopenia from ineffective hematopoiesis, dysplasia in single or multiple lineages, and transformation to acute leukemia in a subset of patients. The genomic landscape revealed by next-generation sequencing has provided a comprehensive picture of the molecular pathways involved in MDS pathogenesis. Recurrent mutational targets in MDS are the genes involved in RNA splicing, DNA methylation, histone modification, transcription, signal transduction, cohesin complex and DNA repair. Sequential acquisition of mutations in these sets of genes serves as a driver for the initiation, clonal evolution and progression of MDS. Based on these findings, novel agents targeting driver mutations of MDS are currently under development and expected to improve the clinical outcome of MDS in the coming decades.