Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner
文献类型：期刊论文
| 作者 | Man, Na5; Tan, Yurong5; Sun, Xiao-Jian5; Liu, Fan5; Cheng, Guoyan5; Greenblatt, Sarah M.5; Martinez, Camilo5; Karl, Daniel L.5; Ando, Koji5; Xu, Mingjiang3,5 |
| 刊名 | BLOOD
 |
| 出版日期 | 2017 |
| 卷号 | 129期号:20页码:2782-2792 |
| 关键词 | IL-6 Tocilizumab Inflammation NLRP3 inflammasome IL-17A Biologics |
| ISSN号 | 0006-4971 |
| DOI | 10.1182/blood-2016-10-745034 |
| 文献子类 | Article |
| 英文摘要 | AML1-ETO (AE), a fusion oncoprotein generated by t(8; 21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy inAMLand demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. |
| 学科主题 | Hematology |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; POTENT ANTITUMOR-ACTIVITY ; T-LYMPHOCYTE STIMULATION ; NF-KAPPA-B ; FUSION PROTEIN ; STEM-CELL ; MONITORING AUTOPHAGY ; HEMATOPOIETIC STEM ; APOPTOSIS ; DIFFERENTIATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000401523300010 |
| 出版者 | AMER SOC HEMATOLOGY |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/912]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA, 2.Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai, Peoples R China; 3.Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA; 4.Shanghai Jiao Tong Univ, Sch Med, Chinese Acad Sci, Inst Hlth Sci,Shanghai Inst Biol Sci, Shanghai, Peoples R China; 5.Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA; |
| 推荐引用方式 GB/T 7714 | Man, Na,Tan, Yurong,Sun, Xiao-Jian,et al. Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner[J]. BLOOD,2017,129(20):2782-2792. |
| APA | Man, Na.,Tan, Yurong.,Sun, Xiao-Jian.,Liu, Fan.,Cheng, Guoyan.,...&,.(2017).Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner.BLOOD,129(20),2782-2792. |
| MLA | Man, Na,et al."Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner".BLOOD 129.20(2017):2782-2792. |
入库方式： OAI收割
来源：上海营养与健康研究所
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