Understanding MDS stem cells: Advances and limitations.

In work spanning several decades, extensive studies have focused on the properties of malignant stem cells that drive the pathogenesis of acute myeloid leukemia (AML). However, relatively little attention has been devoted to several serious myeloid malignancies that occur prior to the onset of frank leukemia, including myelodysplastic syndrome (MDS). Like leukemia, MDS is hypothesized to arise from a pool of immature malignant stem and progenitor cells (MDS-SCs) that serve as a reservoir for disease evolution and progression¹. While multiple studies have sought to identify and characterize the biology and vulnerabilities of MDS-SCs, yet translation of scientific concepts to therapeutically impactful regimens has been limited. Here, we evaluate the currently known properties of MDS-SCs as well as the post-transcriptional mechanisms that drive MDS pathogenesis at a stem and progenitor level. We highlight limits and gaps in our characterization and understanding of MDS-SCs and address the extent to which the properties of MDS-SC are (and can be) inferred from the characterization of LSCs.