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CYB561A3 is the Key Lysosomal Iron Reductase Required for Burkitt B-cell Growth and Survival.

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资源类型：
Pubmed体系：
作者：
Zhonghao Wang[1,2,3,4] ; Rui Guo[1,2,3] ; Stephen J. Trudeau[1,2,3] ; Emma Wolinsky[1,2,3] ; Tslil Ast[2,5] ; Jin Hua Liang[1,2,3] ; Chang Jiang[1,2,3,6] ; Yijie Ma[1,2,3] ; Mingxiang Teng[7] ; Vamsi K. Mootha and[2,5] ; Benjamin E. Gewurz[1,2,3] ;
机构： [1]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston MA 02115, USA [2]Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States of America [3]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA [4]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China [5]Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02115 USA [6]Present address, Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA [7]Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
出处：
DOI： 10.1182/blood.2021011079
ISSN：

关键词： iron metabolism ascorbate transferrin lymphocyte lymphoma iron-sulfur cluster CRISPR screen reactive oxygen species Cytochrome 561 HIF1 alpha ferroptosis

摘要：
Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma, the leading childhood cancer in sub-Saharan Africa. Burkitt cells retain aspects of germinal center B-cell physiology with MYC-driven B-cell hyperproliferation, yet little is presently known about their iron metabolism. CRISPR/Cas9 analysis highlighted the little studied ferrireductase CYB561A3 as critical for Burkitt proliferation, but not for that of closely related EBV-transformed lymphoblastoid cells or nearly all other Cancer Dependency Map cell lines. Burkitt CYB561A3 knockout induced profound iron starvation, despite ferritinophagy and plasma membrane transferrin upregulation. Elevated concentrations of ascorbic acid, a key CYB561 family electron donor or the labile iron source ferrous citrate rescued Burkitt CYB561A3 deficiency. CYB561A3 knockout caused catastrophic lysosomal and mitochondrial damage and impaired mitochondrial respiration. By contrast, lymphoblastoid B-cells with the transforming EBV latency III program were instead dependent on the STEAP3 ferrireductase. These results highlight CYB561A3 it as an attractive therapeutic Burkitt lymphoma target.Copyright © 2021 American Society of Hematology.

基金：
NIH RO1s AI137337 and CA228700 (BEG), Starr Cancer Foundation Project # I11-0043, Burroughs Wellcome Career Award in Medical Sciences and an American Cancer Society Research Scholar Award (BEG), Howard Hughes Medical Institute (VKM) and a Lymphoma Research Foundation award to R.G. RNAseq data was deposited in NIH GEO Omnibus, GSE149066 and will be released upon publication.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 1 区 血液学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 血液学
第一作者：
第一作者机构： [1]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston MA 02115, USA [2]Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States of America [3]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA [4]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构： [1]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston MA 02115, USA [2]Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States of America [3]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
推荐引用方式(GB/T 7714)：
Zhonghao Wang,Rui Guo,Stephen J. Trudeau,et al.CYB561A3 is the Key Lysosomal Iron Reductase Required for Burkitt B-cell Growth and Survival.[J].Blood.2021,138(22):2216-2230.doi:10.1182/blood.2021011079.
APA：
Zhonghao Wang,Rui Guo,Stephen J. Trudeau,Emma Wolinsky,Tslil Ast...&Benjamin E. Gewurz.(2021).CYB561A3 is the Key Lysosomal Iron Reductase Required for Burkitt B-cell Growth and Survival..Blood,138,(22)
MLA：
Zhonghao Wang,et al."CYB561A3 is the Key Lysosomal Iron Reductase Required for Burkitt B-cell Growth and Survival.".Blood 138..22(2021):2216-2230

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