Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia

doi:10.1016/j.bbrc.2021.02.027

	Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia
	Zhang, Youping 1; Luo, Ting 2; Ding, Xinyu3 ; Chang, YungTing 4; Liu, Chuanxu 1; Zhang, Yongqiang 2; Hao, Siguo 1; Yin, Qianqian3 ; Jiang, Biao3,5
	2021-04-02
发表期刊	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (IF:2.5[JCR-2023],2.7[5-Year])
ISSN	0006-291X
EISSN	1090-2104
卷号	547 页码:162-168
发表状态	已发表
DOI	10.1016/j.bbrc.2021.02.027
摘要	Although acute myeloid leukemia (AML) is a highly heterogeneous disease with diverse genetic subsets, one hallmark of AML blasts is myeloid differentiation blockade. Extensive evidence has indicated that differentiation induction therapy represents a promising treatment strategy. Here, we identified that the pharmacological inhibition of the mitochondrial electron transport chain (ETC) complex III by antimycin A inhibits proliferation and promotes cellular differentiation of AML cells. Mechanistically, we showed that the inhibition of dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme in de novo pyrimidine biosynthesis, is involved in antimycin A-induced differentiation. The activity of antimycin A could be reversed by supplement of excessive amounts of exogenous uridine as well as orotic acid, the product of DHODH. Furthermore, we also found that complex III inhibition exerts a synergistic effect in differentiation induction combined with DHODH inhibitor brequinar as well as with the pyrimidine salvage pathway inhibitor dipyridamole. Collectively, our study uncovered the link between mitochondrial complex III and AML differentiation and may provide further insight into the potential application of mitochondrial complex III inhibitor as a mono or combination treatment in differentiation therapy of AML. (c) 2021 Published by Elsevier Inc.
关键词	Acute myeloid leukemia Differentiation therapy Mitochondrial ETC complex III Pyrimidine biosynthesis
收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000624915400008
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126083
专题	免疫化学研究所_特聘教授组_抗体化学实验室生命科学与技术学院_博士生
通讯作者	Hao, Siguo; Yin, Qianqian; Jiang, Biao
作者单位	1.Shanghai Jiao Tong Univ, Dept Hematol, Xin Hua Hosp, Sch Med, Shanghai 200092, Peoples R China; 2.East China Univ Sci & Technol, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China; 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; 4.Shanghai Jiao Tong Univ, Renji Hosp, Dept Pharm, Sch Med, Shanghai 200127, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Organ Chem, CAS Key Lab Synthet Chem Nat Subst, 345 Lingling Rd, Shanghai 200032, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Zhang, Youping,Luo, Ting,Ding, Xinyu,et al. Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2021,547:162-168.
APA	Zhang, Youping.,Luo, Ting.,Ding, Xinyu.,Chang, YungTing.,Liu, Chuanxu.,...&Jiang, Biao.(2021).Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,547,162-168.
MLA	Zhang, Youping,et al."Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 547(2021):162-168.