Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [drug]

In this study we report that during evolution of MDS malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment shows a profound activation of protein synthesis machinery and increased oxidative phosphorylation that occurs during later stages of MDS pathogenesis. Reliance on protein synthesis makes MDS stem cells senstive to translation inhibitors including homoharringtonine. Overall design: Respective populations were sorted from human bone marrow mononuclear cells, treated with Homoharringtonine for 4 hours at 250 nM and total RNA is isolated and subjected to RNA -seq.