title: 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.
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China; Department of Hematology, No. 202 Hospital of PLA, Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China; Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China; School of Medicine, Nankai University, Tianjin, China.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Hematology, No. 202 Hospital of PLA, Shenyang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Deng
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China; Beijing Shijitan Hospital, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lv
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Daihong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China. Electronic address: liyu301@vip.163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, China. Electronic address: lipingruirui@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Dou
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D017930:Genes, Reporter; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D000075142:RUNX1 Translocation Partner 1 Protein; D056564:Sirtuin 1 / Q000235:genetics*; D015533:Transcriptional Activation; D014178:Translocation, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D056564:Sirtuin 1