Cooperative Gene Repression by DNA Methylation and LSD1-Mediated Enhancer Inactivation in Acute Myeloid Leukemia

Cihangir Duy,Matt Teater,Francine E. Garrett-Bakelman,Tak C. Lee,Cem Meydan,Jacob Lowell Glass,Meng Li,Helai Mohammad,Kimberly Smitheman,Alan H. Shih,Omar Abdel-Wahab,Elisabeth Paietta,Martin S. Tallman,Monica L. Guzman,Ryan G. Kruger,Caretha L. Creasy,Ross L. Levine,Martin Carroll,Ari Melnick

Blood（2016）

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摘要

Epigenetic silencing of tumor suppressor genes, mediated by aberrant DNA hypermethylation and repressive histone modifications, is a hallmark of acute myeloid leukemia (AML). Novel epigenetic therapies are emerging, but single-agent approaches targeting only one category of epigenetic marks have limited therapeutic activity. We show that combinatorial treatment strategy targeting epigenetic modifications of both promoter and enhancer elements can improve therapeutic intervention.

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