Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for progression, suggest that myelodysplastic syndromes encompass a multitude of disorders, likely involving numerous pathologic pathways. In fact, it is the effort to understand the underlying biology of these syndromes that has led to recent advances in treatment approaches, including the FDA approval of three new agents (5-azacitidine, decitabine, and lenalidomide) for the treatment of MDS. This review will present data supporting each of the current pathophysiologic pathways implicated in the development and progression of MDS; summarize the emerging clinical paradigms for treating patients with MDS; and offer insights into several novel approaches attempting to improve treatment options for future MDS patients.

Keywords: Myelodysplastic syndrome, pathophysiology, differentiation therapy, epigenetic therapy, bone marrow transplantation, immunomodulation