Issues

The transformation of myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML) is associated with poor response to therapy and an extremely poor prognosis. The genetic and phenotypic heterogeneity of the expanded hematopoietic progenitor cell types throughout this process may provide insight into the clonal features that promote progression. On p. 316, Guess et al. leverage single-cell multi-omic technologies to dissect mutational clonality, identifying archetypes of evolution dynamics, each characterized by unique patterns of mutated pathways. Menssen et al., on p. 330, observed high subclonal prevalence of mutations affecting signaling genes, such as FLT3 and RAS genes, during the evolution of MDS to sAML. Although each signaling gene mutant subclone identified was almost exclusively marked by a single signaling gene mutation, nearly half of sAML patients profiled had multiple such mutations present, many with dynamic clonality changes through progression. These findings are In The Spotlight on p. 270 by Romine and van Galen, offering a vision of future personalized therapies targeting transformation-deemed clones. Cover image by Tetiana Vavryk.