Background: Myelodysplastic syndromes (MDS) represent a heterogeneous
group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or
microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS
comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells
differentiation, with the main consequence of peripheral cytopenias and increased risk to
evolution in acute myeloid leukemia (AML).
Method: This review summarizes the evolving understanding of the role of genetic and
epigenetic alterations involved in pathogenesis and current and future strategies for therapeutic
targeting in myelodysplastic syndromes.
Results: In addition to molecular characteristics, immune and microenvironmental factors in
bone marrow of MDS patients may further modify the MDS manifestations, its clinical
presentation, disease course, risk of transformation to AML and prognosis of MDS, as well as response to therapy.
Current clinical response to therapy approaches are exerted both by epigenetic alterations and by induction
Conclusion: Future treatment strategies in preclinical and clinical investigations are directed towards new dosing
schedules of existing drugs, new genetic and epigenetic targets and combination of different agents, including
hypomethylation agents and histone deacetylase inhibitors.