Myelodysplastic syndromes. Contemporary biologic concepts and emerging diagnostic approaches

The myelodysplastic syndromes (MDS) are an enigmatic group of clonal hematopoietic stem cell disorders associated with significant morbidity and mortality. Typically, MDS evolves from an early phase of accelerated apoptosis resulting in ineffective hematopoiesis to a later phase of increasing proliferation with maturation arrest. Afflicted patients experience a deteriorating course characterized by peripheral cytopenia(s) with consequent infection and hemorrhage and, in some cases, progression to acute leukemia. The classification of MDS has been a matter of some controversy, perhaps allied to our largely unsatisfactory insights into the pathobiology of the disease. Recently, however, new concepts have emerged to explain the etiology and pathogenesis of MDS that invoke a model for step-wise genetic progression with modulation by the immune system and the marrow microenvironment. From these insights into its cellular and molecular pathogenesis have emerged new strategies for both diagnosis and treatment. With the implementation of these strategies, it is anticipated that a more rational and objective approach to the diagnosis and classification of MDS may be achieved, affording the use of more effective targeted therapy.