The myelodysplastic syndrome(s): a perspective and review highlighting current controversies

The myelodysplastic syndrome (MDS) includes a diverse group of clonal and potentially malignant bone marrow disorders characterized by ineffective and inadequate hematopoiesis. The presumed source of MDS is a genetically injured early marrow progenitor cell or pluripotential hematopoietic stem cell. The blood dyscrasias that fall under the broad diagnostic rubric of MDS appear to be quite heterogeneous, which has made it very difficult to construct a coherent, universally applicable MDS classification scheme. A recent re-classification proposal sponsored by the World Health Organization (WHO) has engendered considerable controversy. Although the precise incidence of MDS is uncertain, it has become clear that MDS is at least as common as acute myelogenous leukemia (AML). There is considerable overlap between these two conditions, and the former often segues into the latter; indeed, the distinction between AML and MDS can be murky, and some have argued that the current definitions are arbitrary. Despite the discovery of several tantalizing pathophysiological clues, the basic biology of MDS is incompletely understood. Treatment at present is generally frustrating and ineffective, and except for the small subset of patients who exhibit mild marrow dysfunction and low-risk cytogenetic lesions, the overall prognosis remains rather grim. In this narrative review, we highlight recent developments and controversies within the context of current knowledge about this mysterious and fascinating cluster of bone marrow failure states.