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DOI | 10.1038/s41467-019-12254-x |
Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia | |
Jiang, Xi1,2,3; Hu, Chao1,2,4; Ferchen, Kyle1; Nie, Ji5; Cui, Xiaolong5; Chen, Chih-Hong6; Cheng, Liting7; Zuo, Zhixiang1,8; Seibel, William9; He, Chunjiang10; Tang, Yixuan7; Skibbe, Jennifer R.1; Wunderlich, Mark11; Reinhold, William C.12; Dong, Lei1,3; Shen, Chao1,3; Arnovitz, Stephen2; Ulrich, Bryan2; Lu, Jiuwei1; Weng, Hengyou1,2,3; Su, Rui1,3; Huang, Huilin1,3; Wang, Yungui1,2,4; Li, Chenying1,3,4; Qin, Xi1,3; Mulloy, James11; Zheng, Yi11; Diao, Jiajie1; Jin, Jie4; Li, Chong7; Liu, Paul P.13; He, Chuan5; Chen, Yuan6; Chen, Jianjun1,2,3 | |
2019-09-25 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methyl-cytosine dioxygenase Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8; 21) AML. NSC-311068 and especially NSC-370284 significantly repressed TET1-high AML progression in vivo. UC-514321, a structural analog of NSC-370284, exhibited a more potent therapeutic effect and prolonged the median survival of TET1-high AML mice over three fold. NSC-370284 and UC-514321 both directly target STAT3/5, transcriptional activators of TET1, and thus repress TET1 expression. They also exhibit strong synergistic effects with standard chemotherapy. Our results highlight the therapeutic potential of targeting the STAT/TET1 axis by selective inhibitors in AML treatment. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417884500005 |
WOS关键词 | MLL-REARRANGED LEUKEMIA ; STEM-CELLS ; SIGNALING PATHWAY ; B-CELL ; TET1 ; RESISTANCE ; CANCER ; STAT3 ; ACTIVATION ; ADULTS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204557 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Cincinnati, Dept Canc Biol, Cincinnati, OH 45219 USA; 2.Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA; 3.City Hope Natl Med Ctr, Beckman Res Inst, Dept Syst Biol, Monrovia, CA 91016 USA; 4.Zhejiang Univ, Affiliated Hosp 1, Dept Hematol, Hangzhou 310003, Zhejiang, Peoples R China; 5.Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, Dept Chem,Dept Biochem & Mol Biol, 5841 S Maryland Ave, Chicago, IL 60637 USA; 6.City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA; 7.Southwest Univ, Coll Pharmaceut Sci, Minist Educ, Key Lab Luminescence & Real Time Analyt Chem, Chongqing 400715, Peoples R China; 8.Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China; 9.Cincinnati Childrens Hosp Med Ctr, Div Oncol, Cincinnati, OH 45229 USA; 10.Wuhan Univ, Sch Basic Med Sci, Wuhan 430071, Peoples R China; 11.Cincinnati Childrens Hosp Med Ctr, Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA; 12.NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA; 13.NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA |
推荐引用方式 GB/T 7714 | Jiang, Xi,Hu, Chao,Ferchen, Kyle,et al. Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Jiang, Xi.,Hu, Chao.,Ferchen, Kyle.,Nie, Ji.,Cui, Xiaolong.,...&Chen, Jianjun.(2019).Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia.NATURE COMMUNICATIONS,8. |
MLA | Jiang, Xi,et al."Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia".NATURE COMMUNICATIONS 8(2019). |
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