ArticleThe Journal of clinical investigation2022
Dissecting stepwise mutational impairment of megakaryopoiesis in a model of Down syndrome-associated leukemia.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Individuals with Down syndrome (DS) have more than 100-fold increased risk of acute megakaryoblastic leukemia (AMKL), but its pathogenesis is poorly understood. In this issue of the JCI, Arkoun et al. engineered stepwise DS-AMKL-associated mutations in GATA1, MPL, and SMC3 in human induced pluripotent stem cell (iPSC) clones from individuals with DS to dissect how each mutation affects gene expression control and megakaryocytic differentiation. The authors showed that the mutations cooperatively promote progression from transient myeloproliferative disorder to DS-AMKL. This study highlights the importance of mutation order and context in the perturbations of transcriptional and differentiation pathways involved in the evolution of hematologic malignancies, which will be critical for the development of preventative and therapeutic interventions.
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