Myelodysplastic Syndromes: Pathophysiology

Myelodysplastic syndromes (MDS) describe a heterogeneous and complex group of clonal bone marrow failure disorders characterized by ineffective hematopoiesis, peripheral cytopenias, morphologic dysplasia, and cellular dysfunction, often leading to increased risk of infection and transfusion requirements. They typically represent diseases of the elderly, and, while sometimes linked to known environmental exposures, are usually characterized as idiopathic. Understanding MDS pathogenesis is crucial to the development of biologically targeted therapies. This chapter explores MDS pathogenesis theories in terms of (1) the MDS cell of origin; (2) genetic alterations within the cell of origin; (3) alterations in bone marrow microenvironment and apoptosis; (4) alterations in immune surveillance; and (5) functional cellular abnormalities.