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Heart failure drug proscillaridin A targets MYC overexpressing leukemia through global loss of lysine acetylation.

Da Costa EM, Armaos G, McInnes G, Beaudry A, Moquin-Beaudry G, Bertrand-Lehouillier V, Caron M, Richer C, St-Onge P, Johnson JR, Krogan N, Sai Y, Downey M, Rafei M, Boileau M, Eppert K, Flores-Díaz E, Haman A, Hoang T, Sinnett D, Beauséjour C, McGraw S, Raynal NJ

Département de pharmacologie et physiologie, Université de Montréal, Montréal, (Québec), Canada.

Cardiac glycosides are approved for the treatment of heart failure as Na+/K+ pump inhibitors. Their repurposing in oncology is currently investigated in preclinical and clinical studies. However, the identification of a specific cancer type defined by a molecular signature to design targeted clinical trials with cardiac glycosides remains to be characterized. Here, we demonstrate that cardiac glycoside proscillaridin A specifically targets MYC overexpressing leukemia cells and leukemia stem cells by causing MYC degradation, epigenetic reprogramming and leukemia differentiation through loss of lysine acetylation.

J. Exp. Clin. Cancer Res. 2019;38(1):251.

Pubmed ID: 31196146

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