Karmen Stankov, Suncica Stankov and Jasmina Katanic Pages 135 - 169 ( 35 )
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 of apoptosis. 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.Myelodysplastic syndromes, leukemia, mutations, epigenetic targets, pathogenesis, therapy, hypomethylating agents, microRNA.
Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 1, 21000 Novi Sad, Vojvodina