Loss of Dnmt3b accelerates MLL-AF9 leukemia progression

doi:10.1038/leu.2016.112

CORC > 北京大学 > 生命科学学院

	Loss of Dnmt3b accelerates MLL-AF9 leukemia progression
	Zheng, Y. ; Zhang, H. ; Wang, Y. ; Li, X. ; Lu, P. ; Dong, F. ; Pang, Y. ; Ma, S. ; Cheng, H. ; Hao, S. ; Tang, F. ; Yuan, W. ; Zhang, X. ; Cheng, T.
刊名	LEUKEMIA
	2016
关键词	ACUTE MYELOID-LEUKEMIA HEMATOPOIETIC STEM-CELLS GENE-EXPRESSION PROFILES HEMATOLOGICAL MALIGNANCIES DNA METHYLTRANSFERASE-1 POTENT INHIBITOR CANCER METHYLATION TRANSFORMATION MUTATIONS
DOI	10.1038/leu.2016.112
英文摘要	Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. Abnormal DNA methylation is involved in the initiation and progression of AML. The de novo methyltransferases Dnmt3a and Dnmt3b are responsible for the generation of genomic methylation patterns. While DNMT3A is frequently mutated in hematological malignancies, DNMT3B is rarely mutated. Although it has been previously reported that Dnmt3b functions as a tumor suppressor in a mouse model of Myc-induced lymphomagenesis, its function in AML is yet to be determined. In this study, we demonstrated that deletion of Dnmt3b accelerated the progression of MLL-AF9 leukemia by increasing stemness and enhancing cell cycle progression. Gene profiling analysis revealed upregulation of the oncogenic gene set and downregulation of the cell differentiation gene set. Furthermore, loss of Dnmt3b was able to synergize with Dnmt3a deficiency in leukemia development. Taken together, these results demonstrate that Dnmt3b plays a tumor suppressive role in MLL-AF9 AML progression, thereby providing new insights into the roles of DNA methylation in leukemia development.; Ministry of Science and Technology of China [2016ZY05002341, 2011CB964800, 2013CB966902, 2015CB964400]; National Natural Science Foundation of China [81421002, 81430004, 81330015, 91519315, 81300374, 81300375, 81400077, 81500085]; SCI(E); PubMed; ARTICLE; chengtao@ihcams.ac.cn; 12; 2373-2384; 30
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/433886]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zheng, Y.,Zhang, H.,Wang, Y.,et al. Loss of Dnmt3b accelerates MLL-AF9 leukemia progression[J]. LEUKEMIA,2016.
APA	Zheng, Y..,Zhang, H..,Wang, Y..,Li, X..,Lu, P..,...&Cheng, T..(2016).Loss of Dnmt3b accelerates MLL-AF9 leukemia progression.LEUKEMIA.
MLA	Zheng, Y.,et al."Loss of Dnmt3b accelerates MLL-AF9 leukemia progression".LEUKEMIA (2016).