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

• SIRT1 is highly expressed in t(8;21) acute myeloid leukemia.
• AML1–ETO triggers the activation of SIRT1 by binding to SIRT1 promoter.
• SIRT1 inhibition reduces proliferation in the AML1–ETO-positive leukemia cells.

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.