Molecular mechanisms in myelodysplastic syndromes and implications for evolution to acute leukemias

This article reviews the molecular lesions that occur in the clonal hematop oietic disorders classified as myelodysplastic syndromes (MDS). A systemati zation of these molecular lesions is attempted based on the types of molecu lar abnormalities. Characteristically, these molecular lesions affect pluri potent hematopoietic progenitors and therefore affect myeloid, monocytic, e rythroid, and megakaryocytic lineages. Progression of MDS to acute myelogen ous leukemia is common; transformation is considered the final stage in the multi-step process of accumulation of molecular lesions over a prolonged l atency period of MDS evolution. Although no molecular lesion is MDS specifi c, multiple combinations of molecular lesions are common and a systematic a pproach based on the type of molecular abnormality may offer a better under standing of MDS pathogenesis and the basis for new therapeutic strategies.