AML1-ETO promotes SIRT1 expression to enhance leukemogenesis of t(8;21) acute myeloid leukemia

Recently, SIRT1 was found to play an important role in a variety of solid and hematologic malignancies. The expression and function of SIRT1 may differ completely depending on cell type and gene subtype, and it can act as a tumor suppressor or oncogene. We describe how SIRT1 mRNA and protein levels are overexpressed in t(8;21) AML cells. AML1-ETO triggers the activation of SIRT1 by binding at AML1 binding sites on the SIRT1 promoter. Pharmacologic targeting or RNAi-mediated inhibition of SIRT1 induces G1 arrest, apoptosis, and proliferation inhibition that is more sensitive in AML1-ETO-positive than AML1-ETO-negative cell lines. Our data suggest that targeting SIRT1 may be an attractive therapeutic strategy in t(8;21) AML. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.Beijing Nova Program [2011114]; National Natural Science Foundation of China [30800482, 30971297, 81102242, 81000221, 81270610, 81470010, 81170518, 81370666, 90919044]; Beijing Natural Science Foundation of China [7102147, 7132217]; High and New Technology Program of the PLA [2010gxjs091]; Capital Medical Development Scientific Research Fund [2007-2040]; National Public Health Grand Research Foundation [201202017]; funding of the public health project [Z111107067311070]; National 973 Project of China [2005CB522400]SCI(E)PubMedARTICLE62-694