Review Series BONE MARROW FAILURE Recent developments in myelodysplastic syndromes

The myelodysplastic syndromes (MDS) represent the most common class of acquired bonemarrow failure syndromes in adults. Although MDSs are increasinglywell understood from a biological standpoint, including discovery of .40 MDS-associated recurrently mutated genes in the last 7 years, improved pathological insight has not yet translated into highly effective or curative therapies for most patients suffering from these disorders. Collectively, the term MDS describes a diverse group of clonal disorders of hematopoietic stem or progenitor cells characterized by ineffective hematopoiesis, abnormal “dysplastic” cell morphology, and potential for clonal evolution. Increasing failure of cellular differentiation is associated with evolution to secondary acute myeloid leukemia (AML), currently arbitrarily defined by the World Health Organization (WHO) as$20%myeloid blasts in the blood or marrow, or the presence of one of several AML-defining karyotypic abnormalities [eg, t(15;17), t(8;21), inv(16), or t(16;16)] regardless of blast proportion. AML is ultimately diagnosed in up to 30% of MDS cases. In this review, we describe recent advances in our collective understanding of the genetic basis of MDS in the context of existing knowledge and survey how thesefindingsmay contribute to improvements in diagnosis and prognostic assignment of patients, serve as predictors or biomarkers of response to treatment, and aid development of future therapies. MDS cell biology and immunobiology, animal models, the contribution of the marrow microenvironment to MDS development and persistence, and familial predisposition to MDS are also areas of active development but are beyond the scope of this review.