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

作者：Zhou, Lei; Wang, Qian; Chen, Xiaosu; Fu, Lin; Zhang, Xiaodong; Wang, Lijun; Deng, Ailing; Li, Dandan; Liu, Jing; Lv, Na; Wang, Lili; Li, Yonghui; Liu, Daihong; Yu, Li^*; Dou, Liping^*

来源：Experimental Hematology, 2017, 46: 62-69.

DOI：10.1016/j.exphem.2016.09.013

• HISTONE DEACETYLASE
• BINDING-SITES
• GENOME-WIDE
• ACTIVATION
• CELLS
• TRANSCRIPTION
• P53
• DIFFERENTIATION
• ACETYLATION
• INTERPLAY

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.

• 出版日期2017-2
• 单位南开大学; 南京大学; 中国人民解放军第二O二医院; 北京大学; 中国人民解放军总医院