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| 1 | MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages显示文摘Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of inflammation.Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.The expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were determined.Macrophage phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying mechanisms.The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment.The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages.Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of MST4.In a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of thrombocytopenia.Downregulation of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of macrophages.Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP. | Jingjing Cao Lili Ji Yanxia Zhan Xia Shao Pengcheng Xu Boting Wu Pu Chen Luya Cheng Xibing Zhuang Yang Ou Fanli Hua Lihua Sun Feng Li Hao Chen Zhaocai Zhou Yunfeng Cheng | 2023 | Cellular & Molecular Immunology2023，20，12： | 0 |
| 2 | Author Correction:MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages显示文摘In this article,the details for Affiliation 1 were incorrectly given as‘Department of Hematology,Fudan University,Shanghai 200032,China’but should have been‘Department of Hematology,Zhongshan Hospital,Fudan University,Shanghai 200032,China’;the details for Affiliation 3 were incorrectly given as‘Department of Transfusion Medicine,Fudan University,Shanghai 200032,China’but should have been‘Department of Transfusion Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China’;the details for Affiliation 4 were incorrectly given as‘Department of Laboratory Medicine,Fudan University,Shanghai 200032,China’but should have been‘Department of Laboratory Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China’.The original article has been corrected. | Jingjing Cao Lili Ji Yanxia Zhan Xia Shao Pengcheng Xu Boting Wu Pu Chen Luya Cheng Xibing Zhuang Yang Ou Fanli Hua Lihua Sun Feng Li Hao Chen Zhaocai Zhou Yunfeng Cheng | 2023 | Cellular & Molecular Immunology2023，20，12： | 0 |
| 3 | Prevalence and Clinical Implication of t(11;14)in Light-Chain Amyloidosis with or without Coexistent Multiple Myeloma in the Era of Proteasome Inhibitors显示文摘Background Light-chain amyloidosis(AL)and multiple myeloma(MM)may coexist in some patients and,although they share some cytogenetic abnormalities,they usually present with different clinical phenotypes.Translocation(11;14)is the most common cytogenetic abnormality in AL,but the prevalence and clinical implication of t(11;14)in patients with AL,with or without coexistent MM,remains unclear.Methods A total of 119 consecutive newly diagnosed AL patients with available fluorescence in situ hybridization(FISH)data were retrospectively included and classified as primary AL alone(pAL-alone)or AL with coexistent MM(AL-MM).Clinical characteristics,FISH profiles,and hematologic and survival outcomes were analyzed.Results There were 53 patients in the pAL-alone group and 66 in the AL-MM group.The prevalence of t(11;14)was significantly higher in the pAL-alone group than the AL-MM group(49.1%vs.26.2%,P=0.012).A significantly higher proportion of the pAL-alone group achieved hematologic response compared with the AL-MM group(60.4%vs.39.4%,P=0.023).Patients with AL-MM experienced significantly shorter hematologic event-free survival(hemEFS)than those with pAL-alone(median,4.8 months vs.44.3 months,P<0.001),as well as significantly shorter overall survival(OS;median,15.2 months vs.not reached,P<0.001).When stratified by the presence or absence of coexistent MM and t(11;14),AL-MM patients with t(11;14)had the worst hemEFS(median,3.8 months,P<0.001)and OS(median,5.4 months,P=0.001).Conclusions Patients with pAL-alone had a higher prevalence of t(11;14)than those with AL-MM.The AL-MM group had poorer outcomes,despite the availability of proteasome inhibitor treatment,with AL-MM patients with t(11;14)showing the worst outcomes.Better diagnostic and treatment approaches are warranted for this population. | Tianhong XU Zheng WEI Jing LI Jiadai XU Yang YANG Wenjing WANG Jingli ZHUANG Zhimei WANG Lili JI Luya CHENG Weiguang WANG Zhixiang CHENG Yang KE Ling YUAN Peng LIU | 2022 | Clinical Cancer Bulletin2022，1，1： | 0 |
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