Issues
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Cover Image
Cover Image
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. - PDF Icon PDF LinkTable of Contents
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In This Issue
Obituary
In the Spotlight
Perspective
Perspectives on the Risk-Stratified Treatment of Multiple Myeloma
Research Brief
In Vivo Monitoring of Polycythemia Vera Development Reveals Carbonic Anhydrase 1 as a Potent Therapeutic Target
A focal model of PV development reveals its invasion of distant organ sites, dependency on the spleen, and carbonic anhydrase 1 as a potential therapy target.
Research Articles
Type I but Not Type II Calreticulin Mutations Activate the IRE1α/XBP1 Pathway of the Unfolded Protein Response to Drive Myeloproliferative Neoplasms
Loss of Ca2+ binding causes ER stress and creates a unique dependency on the IRE1α/XBP1 pathway in type I and not type II mutant CALR-driven MPNs
Distinct Patterns of Clonal Evolution Drive Myelodysplastic Syndrome Progression to Secondary Acute Myeloid Leukemia
Multimodal single-cell profiling reveals clonal architecture and genetic drivers in the progression of MDS to AML.
Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression
Somatic signaling gene mutations occur frequently in MDS and undergo complex patterns of clonal evolution during progression to secondary AML. The presence of these mutations at MDS is associated with an increased risk of AML progression.
The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and TET2-Mutant Preleukemia
Genome-wide landscape of 5hmC and cellular phenotypes in human hematopoiesis uncover epigenetic programs governing expansion of TET2-mutant clones, which can be countered by Vitamin C and azacitidine, offering insights into the mechanisms of TET-dependent clonal hematopoiesis.
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