Myelodysplastic syndromes (MDS) are a group of myeloid neoplasms characterized by clonal hematopoiesis and abnormal maturation of hematopoietic cells, resulting in cytopenias. The transformation of MDS to acute myeloid leukemia (AML) reflects a progressive increase in blasts due to impaired maturation of the malignant clone, and thus MDS and many AML subtypes form a biological continuum rather than representing two distinct diseases. Recent data suggest that, in addition to previously described translocations, NPM1 mutations and KMT2A rearrangements are also AML-defining genetic alterations that lead to rapid disease progression, even if they present initially with less than 20% blasts. While some adult patients <20% blasts can be treated effectively with intensive AML-type chemotherapy, in the future, treatment of individual patients in this MDS/AML group will likely be dictated by genetic, biological, and patient-related factors rather than an arbitrary blast percentage.
