文献类型：期刊文献

英文题名：Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia

作者：Chen, Chiqi[1];Hao, Xiaoxin[1];Lai, Xiaoyun[1];Liu, Ligen[1];Zhu, Jun[2];Shao, Hongfang[3];Huang, Dan[1];Gu, Hao[1];Zhang, Tinghua[1];Yu, Zhuo[1];Xie, Li[1];Zhang, Xiaocui[2];Yang, Yi[4];Xu, Jun[5];Zhao, Yuzheng[4,6];Lu, Zhigang[7,8];Zheng, Junke[1,9]

机构：[1]Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Fac Basic Med,Chinese Minist Educ, Hongqiao Int Inst Med,Sch Med,Key Lab Cell Differ, Shanghai 200025, Peoples R China;[2]Shanghai Zhaxin Hosp, Dept Hematol, Shanghai 200434, Peoples R China;[3]Shanghai Sixth Peoples Hosp, Ctr Reprod Med, 600 Yishan Rd, Shanghai 200233, Peoples R China;[4]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ct, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]Tongji Univ, East Hosp, Sch Med, Shanghai 200120, Peoples R China;[6]Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing, Peoples R China;[7]Fudan Univ, Peoples Hosp Shanghai 5, Shanghai, Peoples R China;[8]Fudan Univ, Inst Biomed Sci, Minist Sci & Technol, Shanghai Key Lab Med Epigenet,Int Colab Med Epige, Shanghai, Peoples R China;[9]Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Reprod Med, Shanghai 200025, Peoples R China

年份：2021

卷号：7

期号：11

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20211110084958);WOS:【SCI-EXPANDED(收录号:WOS:000628616300010)】；

基金：This work was supported by grants from National Basic Research Program of China (2019YFA0801800, 2018YFA0107000, and 2019YFA0904800), National Natural Science Foundation of China (NSFC) (81825001, 81570093, 31971052, 81900147, 81461138037, 31722033, 32030065, 31671484, 81873438, and 82000147), the innovative group of NSFC (81721004), Shanghai Science and Technology Commission (19XD1422100, 17ZR1415500, and 20JC1412000), The National Major Scientific and Technological Special Project for "Significant new drugs development" (2018ZX09201002-005), Research Unit of New Techniques for Live-Cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019RU01, 2019-I2M-5-013), Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone (Stem Cell Strategic Biobank and Stem Cell Clinical Technology Transformation Platform, ZJ2018-ZD-004), innovative research team of high-level local universities in Shanghai.

语种：英文

外文关键词：Diseases - Phosphorylation - Chemotherapy - Metabolism - Electric resistance - Cells - Cytology

摘要：How metabolic status controls the fates of different types of leukemia cells remains elusive. Using a SoNar-transgenic mouse line, we demonstrated that B cell acute lymphoblastic leukemia (B-ALL) cells had a preference in using oxidative phosphorylation. B-ALL cells with a low SoNar ratio (SoNar-low) had enhanced mitochondrial respiration capacity, mainly resided in the vascular niche, and were enriched with more functional leukemia-initiating cells than that of SoNar-high cells in a murine B-ALL model. The SoNar-low cells were more resistant to cytosine arabinoside (Ara-C) treatment. cyclic adenosine 3',5'-monophosphate response element-binding protein transactivated pyruvate dehydrogenase complex component X and cytidine deaminase to maintain the oxidative phosphorylation level and Ara-C-induced resistance. SoNar-low human primary B-ALL cells also had a preference for oxidative phosphorylation. Suppressing oxidative phosphorylation with several drugs sufficiently attenuated Ara-C-induced resistance. Our study provides a unique angle for understanding the potential connections between metabolism and B-ALL cell fates.