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Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia

查看全文 作　　者：Liang [1]Huang;Dan [19]Liu;Na [1]Wang;Shaoping [19,18]Ling;Yuting [1]Tang;Jun [19]Wu;Lingtong [19,4,16]Hao;Hui [1]Luo;Xuelian [1]Hu;Lingshuang [1]Sheng;Lijun [1]Zhu;Di [1]Wang;Yi [1]Luo;Zhen [1]Shang;Min [1]Xiao;Xia [1]Mao;Kuangguo [1]Zhou;Lihua [19,16]Cao;Lili [19]Dong;Xinchang [19,4]Zheng;Pinpin [19,4]Sui;Jianlin [19]He;Shanlan [19,4]Mo;Jin [19]Yan;Qilin [2]Ao;Lugui [4]Qiu;Hongsheng [6]Zhou;Qifa [6]Liu;Hongyu [7]Zhang;Jianyong [8]Li;Jie [9]Jin;Li [10]Fu;Weili [11]Zhao;Jieping [12]Chen;Xin [13]Du;Guoliang [14]Qing;Hudan [14]Liu;Xin [2,5]Liu;Gang [15,16]Huang;Ding [17,18]Ma;Jianfeng [1,3,18]Zhou;Qian-fei [19,3,4]Wang 高影响力作者 机构地区：[1]Department of Hematology, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan,Hubei 430030, China;[2]Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and De-velopment, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;[3]Department of Pathology, TongjiHospital, Tongji Medical College, Huazhong University of Seience and Technology, Wuhan, Hubei 430030, China;[4]Institute of He-matology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & PeMng Union Medical College, Tianjin 300020,China;[5]University of Chinese Academy of Sciences, Beijing 100049, China;[6]Department of Hematology, Nanfang Hospital,Southern Medical University, Guangzhou, Guangdong 510515, China;[7]Department of Hematology, Peking University ShenzhenHospital, Shenzhen, Guangdong 518036, China;[8]Department of Hematology, the First Affiliated Hospital of Nanjing Medical Uni-versity and Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China;[9]Department of Hematology, the First Affiliated HospitalZhejiang University College of Medicine, Hangzhou, Zhejiang 310003, China;[10]Department of Hematology, Beijing FriendshipHospital, Capital Medical University, Beijing 100050, China;[11]Shanghai Institute of Hematology, State Key Laboratory of MedicalGenomics, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;[12]Departmentof Hematology, Southwest Hospital Third Military Medical University, Chongqing 400038, China;[13]Department of Hematology,Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China;[14]MedicalResearch Institute, Wuhan University, Wuhan, Hubei 430071, China;[15]Division of Experimental Hematology and Cancer Biology,Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA;[16]Division of Pathology, Cincinnati Children's Hos-pital Medical Center, Cincinnati, OH 45229, USA; 17 Genome Wisdom Inc., Beijing 100195, China;[17]Department of Obstetrics andGynecology, Tongfi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030,China;[18]Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;[19]Key Laboratory of Genomic and Preeision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China高影响力机构 出　　处：《Cell Research》索引2018年第28卷第2期,共15页高影响力期刊 基　　金：Acknowledgments We thank all the faculties and staffs in the Clinical and Laboratory Unit of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology for their clinical and technical support; the Core Genomic Facility of Beijing Institute of Genomics, Chinese Academy of Sciences for the construction and sequencing of libraries; Drs Qing Li and Jiguang Wang for critical reading and valuable comments on the manuscript; Dr Kai Fu for providing the cell line YT. This study was supported by the National Natural Science Foundation of China (81570196 to JZ, 81425003 to QW, 81670152 to Liang H, 81600120 to NW, 81300410 to DW, 81500100 to YL and 81400122 to KZ), the National Key Basic Research Program of China (2014CB542001 to QW), the Key Program of the National Natural Science Foundation of China (81230052 to JZ), the Key Research Program of the Chinese Academy of Sciences (Precious Medicine Research in Chinese Population; KJZD-EW-L14-3 to QW), and the National High Technology Research and Development Program of China (863 program; 2012AA02A507 to JZ and 2014AA020532 to Liang H). 摘　　要：好攻击的 NK 房间白血病(ANKL ) 是在从亚洲的人之中是更流行的 NK 房间瘤的一种稀罕形式并且中央并且南美洲。病人们通常在天以内死到月,甚至在收到迅速的治疗学的管理以后。这里,我们由集成整个染色体执行了 ANKL 的第一全面研究, transcriptome 并且定序指向,象功能的试金一样的 cytokine 数组。在 JAK-STAT 小径的变化在 48% 被识别(14/29 ) ANKL 病人,当细胞外的 STAT3 激发器 IL10 被 56 褶层的一般水准提高时(P < 0.0001 ) 在检查的所有病人的血浆。另外的经常变异的基因包括的 TP53 (34%) , TET2 (28%) , CREBBP (21%) 和 MLL2 (21%) 。耐心的 NK 白血病房间在多重新陈代谢的小径显示出 STAT3 phosphorylation, MYC 表示和 transcriptional 活动的突出的激活。机能上地, STAT3 激活和 MYC 表示为 ANKL 房间的增长和幸存是批评的。发信号的 STAT 调整了发信号的 MYC 抄写节目,和两 STAT, MYC 抄写被要求维持核苷酸合成和 glycolysis 的激活。一起, JAK-STAT 小径在 ANKL 为 genomic 改变和 IL10 刺激代表一个主要目标。这最新发现的 JAK/STAT-MYC-biosynthesis 轴可以在对待白血病的这种子类型为新奇治疗学的策略的发展提供机会。 关 键 词：白血病 房间 JAK-STAT 攻击 识别 STAT3 轴 新陈代谢
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