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

Abstract
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.
AuthorsLei Zhou, Qian Wang, Xiaosu Chen, Lin Fu, Xiaodong Zhang, Lijun Wang, Ailing Deng, Dandan Li, Jing Liu, Na Lv, Lili Wang, Yonghui Li, Daihong Liu, Li Yu, Liping Dou
JournalExperimental hematology (Exp Hematol) Vol. 46 Pg. 62-69 (Feb 2017) ISSN: 1873-2399 [Electronic] Netherlands
PMID27725192 (Publication Type: Journal Article)
CopyrightCopyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • Sirtuin 1
Topics
  • Apoptosis (genetics)
  • Binding Sites
  • Cell Cycle (genetics)
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic (genetics, metabolism)
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, Pair 8
  • Core Binding Factor Alpha 2 Subunit (metabolism)
  • Gene Expression Regulation, Leukemic
  • Genes, Reporter
  • Humans
  • Leukemia, Myeloid, Acute (genetics, metabolism, mortality)
  • Oncogene Proteins, Fusion (metabolism)
  • Prognosis
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Transport
  • RUNX1 Translocation Partner 1 Protein
  • Sirtuin 1 (genetics)
  • Transcriptional Activation
  • Translocation, Genetic

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