Navigating the contested borders between myelodysplastic syndrome and acute myeloid leukemia

Myelodysplastic syndrome and acute myeloid leukemia are heterogeneous myeloid neoplasms which arise from the accumulation of mutations in a myeloid stem cell or progenitor that confer survival or growth advantages. These disease processes are formally differentiated by clinical, laboratory, and morphological presentations, especially with regard to the preponderance of blasts in the peripheral blood or bone marrow (AML); however, they are closely associated through their shared lineage as well as their existence on a spectrum with some cases of MDS displaying increased blasts, a feature that reflects more AML-like behavior, and the propensity for MDS to transform into AML. It is increasingly recognized that the distinctions between these two entities result from the divergent patterns of genetic alterations that drive each of them. Mutations in genes related to chromatin-remodeling and the spliceosome are seen in both MDS and AML arising out of antecedent MDS, while mutations in genes related to signaling pathways such as RAS or FLT3 are more typically seen in AML or otherwise are a harbinger of transformation. In this review, we focus on the insights into the biological and genetic distinctions and similarities between MDS and AML that are now used to refine clinical prognostication, guide disease management, and to inform development of novel therapeutic approaches.

Automated summary

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms resulting from mutations in myeloid stem cells or progenitors. Although they differ in clinical and laboratory presentations, they are closely related through shared lineage and the presence of AML-like features in some MDS cases. Understanding the genetic distinctions and similarities between MDS and AML is crucial for refining prognostication, guiding disease management, and developing novel therapies.