EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma

doi:10.3324/haematol.2019.222935

	EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma
	Xie, Shao 1,2,3,4; Wei, Fan 1,2,5; Sun, Yi-ming 1,2; Gao, Ying-lei 1,2; Pan, Lu-lu 5,6,7; Tan, Min-jia 6,7; Wang, Shu-dong 8; Ding, Jian 1,2; Chen, Yi 1,2
刊名	HAEMATOLOGICA
	2020-04-01
卷号	105 期号:4 页码:1021-1031
ISSN号	0390-6078
DOI	10.3324/haematol.2019.222935
通讯作者	Ding, Jian(jding@simm.ac.cn) ; Chen, Yi(ychen@simm.ac.cn)
英文摘要	Aberrant expression of CDK9/cyclin T1 has been found in diffuse large B-cell lymphoma (DLBCL), and suggests that CDK9 is a poten- tial therapeutic target for DLBCL. Here, we firstly demonstrated that CDKI-73, a novel cydin-dependent kinases (CDK) inhibitor, potently blocks CDK9, triggered apoptosis and dramatically repressed DLBCL cell growth owing to CDK9 inhibition. CDK9 inhibitors specifically elevated the trimethylation of H3K27, which we speculate was due to reduced expression of JMJD3/UTX. Considering the important role of the trimethylation of H3K27 in tumor progression, the synergistic effect of the combination therapy of CDK9 inhibitors with EZH2 inhibitors was investigated. EZH2 inhibitors reversed the upregulation of trimethylation of H3K27, and synergistically inhibited DLBCL and other solid tumors growth in vitro and in vivo. These findings provide a rational basis for the application of CDK9 inhibitors in combination with EZH2 inhibitors in clinical trials.
WOS关键词	CYCLIN-DEPENDENT KINASES ; LYSINE 27 METHYLATION ; SOMATIC MUTATIONS ; DIFFERENTIATION ; TARGET ; PHOSPHORYLATION ; DEREGULATION ; COMBINATION ; COMPLEX ; MCL-1
WOS研究方向	Hematology
语种	英语
出版者	FERRATA STORTI FOUNDATION
WOS记录号	WOS:000522793900035
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280799]
专题	中国科学院上海药物研究所
通讯作者	Ding, Jian; Chen, Yi
作者单位	1.Chinese Acad Sci, Inst Mat Med, Shanghai, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai, Peoples R China 3.Fudan Univ, Key Lab Breast Canc, Shanghai, Peoples R China 4.Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Shanghai Inst Mat Med, Chem Prote Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 7.Chinese Acad Sci, Shanghai, Peoples R China 8.Univ South Australia, Ctr Drug Discovery & Dev, Sch Pharm & Med Sci, Canc Res Inst, Adelaide, SA, Australia
推荐引用方式 GB/T 7714	Xie, Shao,Wei, Fan,Sun, Yi-ming,et al. EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma[J]. HAEMATOLOGICA,2020,105(4):1021-1031.
APA	Xie, Shao.,Wei, Fan.,Sun, Yi-ming.,Gao, Ying-lei.,Pan, Lu-lu.,...&Chen, Yi.(2020).EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma.HAEMATOLOGICA,105(4),1021-1031.
MLA	Xie, Shao,et al."EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma".HAEMATOLOGICA 105.4(2020):1021-1031.