Rise of the Clones: Myelodysplastic Syndrome to Secondary Acute Myeloid Leukemia

Abstract

Myelodysplastic syndrome (MDS) describes a family of blood disorders driven by the clonal expansion of mutated blood cells that can evolve into secondary acute myeloid leukemia (sAML). Two new studies use single-cell and deep sequencing to elucidate the progression of MDS to AML, revealing discrete clonal architectures and the driving role of signaling mutations.

Figure 1.

Schematic detailing the main findings from paired MDS and sAML sequencing. A and B, Three patterns of MDS to sAML clonal evolution are observed by Guess and colleagues, the percentages indicate the proportion of patients following each. Both studies found that progenitor cells acquire mutation types in preferred orders. In the schematic, each cell represents a different clone, and nuclei are color-coded based on driver mutations. C, Both studies classify genetic lesions into functional categories, including epigenetic (e.g., TET2, ASXL1), signaling (e.g., FLT3, NRAS), transcription factor (e.g., GATA2, ETV6), splicing (e.g., U2AF1, SRSF2) and cohesin mutations (e.g., STAG2, RAD21). D, Multiple patterns of clonal evolution of signaling mutations emerged from the work of Menssen and colleagues. The percentages indicate the proportions of patients that follow indicated patterns; the total exceeds 100% because patients can have multiple signaling mutations (which can exhibit all patterns of evolution). Created with BioRender.com.