Zinc finger and BTB domain-containing protein 46 is essential for survival and proliferation of acute myeloid leukemia cell line but dispensable for normal hematopoiesis  

作　　者：Yuan-Yuan Liu Fei-Fei Xiao Bi-Jie Yang Xi Li Shuang-Nian Xu Zhi-Wei Chen Ping Li Yong-Xiu Huang Xue-Mei Fu Xing-Qin Huang Guang-Ling Zheng Jie-Ping Chen Yu Hou 

机构地区：[1]Department of Hematology,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [2]Children's Hospital of Chongqing Medical University,Chongqing 400014,China [3]Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases,College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400016,China [4]Department of Radiology,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China

出　　处：《Chinese Medical Journal》2020年第14期1688-1695,共8页中华医学杂志（英文版）

基　　金：This study was supported by grants from the National Key R&D Program of China(No.2017YFA0106700);Army Major Scientific Research Projects(No.AWS17J007);National Natural Science Foundation of China(No.81670096 and No.81700185);Military Medical Innovation Program(No.SWH2018LJ-07 and No.SWH2018QNKJ-17);and Basic Research Program on Civil-military Integration(No.SWH2017YBXM-06).

摘　　要：Background:Zinc finger and BTB domain-containing protein 46(Zbtb46)is a transcription factor identified in classical dendritic cells,and maintains dendritic cell quiescence in a steady state.Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia(AML).We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells(HSPCs)compared to mature cells,and higher in AML cells compared to normal bone marrow(BM)cells.However,the role of Zbtb46in HSPCs and AML cells remains unclear.Therefore,we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.Methods:We generated Zbtb46^fl/fl and Zbtb46^fl/fl Mx1-Cre mice.The deletion of Zbtb46 in Zbtb46^fl/fl Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly(I).poly(C)(poly(I:C)),and referred as Zbtb46 cKO.After confirming the deletion of Zbtb46,the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry.Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46^fl/fl and Zbtb46 cKO mice.The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas.To investigate the role of Zbtb46 in AML cells,we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46.Cell proliferation rate was determined by cell count assay.Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.Results:The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46^fl/fl littermates(Zbtb46^fl/fl vs.Zbtb46 cKO,HPC:801,310±84,282 vs.907,202±97,403,t=0.82,P=0.46;LSK:86,895±7802 vs.102,210±5025,t=1.65,P=0.17;HSC:19,753±3116 vs.17,608±3508,t=0.46,P=0.67).The repopulation ability of HSCs from Zbtb46^fl/fl Mx1-Cre mice was similar to those from Zbtb46^fl/fl control(P=0.26).Zbtb46 had elevated expression

关 键 词：Zbtb46 transcription factor AML Hematopoietic stem cells 

分 类 号：R733.71[医药卫生—肿瘤]