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.
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Authors | Lei 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 |
Journal | Experimental hematology
(Exp Hematol)
Vol. 46
Pg. 62-69
(Feb 2017)
ISSN: 1873-2399 [Electronic] Netherlands |
PMID | 27725192
(Publication Type: Journal Article)
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Copyright | Copyright © 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
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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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