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Predictive Factors of Renal Damage during Sickle Cell Disease at the hematology-Oncology department of Donka university hospital

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Open Journal of Nephrology 2024年第3期14卷 302-312页

作者： Moussa Traoré Ansoumane Sayon Kanté Marthe Sidibé Mamady Diakité Mohammed Lamine Tégui Camara Foussény Diakité Mamadou Saliou Baldé Ibrahima Chérif Mustapha Komrabai-Kanu Mohammed Lamine Kaba Nephrology-Hemodialysis department of Donka university hospital Conakry Guinea hematology-Oncology department of Donka university hospital Conakry Guinea hematology-Oncology department of Ignace Deen university hospital Conakry Guinea Medical Care Clinic Freetown Sierra-Leone

Introduction: Sickle cell disease, which is the most common hereditary hemoglobinopathy in the world, attacks all body systems, particularly the kidneys. The view of this study was to investigate the predictive factors of kidney damage during sickle cell disease. Materials and methods: It was a retrospective, descriptive and analytical study on files of sickle cell patients hospitalized in the hematology-Oncology department of Donka university hospital during a period from January 1, 2016 to December 31, 2019. Records of sickle cell patients with one or more renal abnormalities were retained. Sickle cell patients without kidney damage were also selected for a comparative study. Only patients without sickle cell disease were excluded. Results: Seventy-five (75) medical records were collected during the study period. From these cases, thirteen (13) records with kidney disease were observed, a frequency of 17%. The mean age of patients was 24.2 years for extremes of 10 and 65 years. The sex ratio was 1.6 in favor of men. The SSFA2 form was the most represented with 92%. 24-hour proteinuria was measured in 13 patients between whom 6 patients (46.2%) had a proteinuria level ≤ 1 g. Eight (8) patients (61.5%) were in stage 1 of chronic kidney disease. The most common type of renal involvement was tubulo-interstitial nephropathy with 8 patients (61.5%). Bivariate analysis showed that elevated serum creatinine (P 2 form of the sickness (P Conclusion: After the observation of an increased serum creatinine and urea, a predominance observation of the SSFA2 form, it should be possible to target patients for whom screening for kidney damage should henceforth be systematic.

关键词： Kidney Damage Predictive Factors Sickle Cell Disease Donka

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Celastrus orbiculatus Extract Inhibits Immune Inflammatory Thrombotic State of B-Lymphoma

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1018-1026页

作者： ZHU Miao SHI Qing-qing NI Jun WU Wei SUN Xing SUN Mei XU Kai-lin LIU Yan-qing GU Jian GU Hao department of hematology Clinical Medical Col ege Yangzhou University Yangzhou Institute of hematology department of hematology The Affiliated Hospital of Xuzhou Medical University department of Oncology The Affiliated Hospital of Yangzhou University Yangzhou University department of Neurology The Affiliated Brain Hospital of Nanjing Medical University

Objective:To investigate the inhibitory effect of Celastrus orbiculatus extracts（COE） on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in ***:The 38B9 lymphoma cells were treated with COE（160μg/mL） and CTX（25 μmol/L）.The apoptosis rate and cell cycle of each group were detected by flow *** secretion of inflammatory factors,including interleukin（IL）-6,IL-10,and tumor necrosis factor α（TNF-α）,in cell supernatant was detected by enzyme-linked immunosorbent assay（ELISA）.In vivo,BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma ***(3 mg·kg-1·d-1) and CTX(40 mg-kg-1·d-1) were administered to the model mice,*** expression of plasma inflammatory factors（IL-6,IL-10 and TNF-α） and thrombus indexes,including D-dimer（D-D）,von Willebrand factor（vWF） and tissue factor（TF）,were detected by ELISA before tumor bearing（1 d）,after tumor formation（14 d） and after intervention（21 d）.PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps（NETs）.Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2（CLEC-2）.The tumor growth and survival of mice were ***:The 38B9 lymphoma cells were apoptotic after the intervention of COE and *** ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells（P<0.05）,and S phase cells decreased in CTX intervented cells（P<0.05）.Also,the secretion level of IL-6 was significantly reduced after COE or CTX intervention（P<0.05）,and IL-10 was significantly increased（P<0.05）.Furthermore,the tumor mass was reduced,and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in nonintervented *** significantly lower levels of TNF-α,IL-6,NETs,TF,DD and CLEC-2,as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice（P

关键词： Celastrus orbiculatus extract immune regulation lymphoma murine lymphoma cells proliferation inhibition thrombotic state tumor inflammation

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Acquired immune thrombotic thrombocytopenic purpura(TTP)associated with inactivated COVID-19 vaccine CoronaVac

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Frontiers of Medicine 2024年第4期18卷 744-751页

作者： Zhangbiao Long Suyu Jiang Honglei Xin Lu Zhang Ruinan Lu Fengqi Liu Yong Xu Linv Wang Jun Wang Xuezhong Zhang Hui liao Jinning Shi Xue Yan Xiang Zhu Ruonan Shao Zijian Li Yilin Zhu Han Yan Jiao Wu Chao Fang Xiaodong Xi Xiaofeng Shi department of hematology The First Affiliated Hospital of Anhui Medical UniversityHefei230022China department of hematology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210003China department of hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing210029China department of hematology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China department of hematology The Affiliated Hospital of Nanjing University of Chinese MedicineThe First Clinical Medical College of Nanjing University of Chinese MedicineNanjing210009China department of hematology Zhongda Hospital of Southeast UniversityNanjing210044China department of hematology Nanjing First HospitalNanjing Medical UniversityNanjing210006China department of hematology The Air Force Hospital of Eastern Theater commandNanjing210016China department of hematology Jiangning Hospital Affiliated of Nanjing Medical UniversityNanjing211199China department of hematology Nanjing Hospital of Chinese MedicineNanjing210006China department of Pharmacology School of Basic MedicineTongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesHuazhong University of Science and TechnologyThe Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei ProvinceWuhan430030China Shanghai Institute of hematology State Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China

Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole *** thrombotic thrombocytopenic purpura(TTP)has been reported after administration of mRNA-or adenoviral vector-based COVID-19 vaccines,including ***2-S,BNT162b2,mRNA-1273,and ChAdOx1 ***,whether inactivated vaccines,such as CoronaVac,could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are *** this study,two cases were *** cases developed TTP after the second CoronaVac vaccination shot,but not the *** demonstrated symptoms of fever,neurological abnormalities,renal dysfunction,thrombocytopenia,and *** patients achieved complete remission through several sessions of plasma exchanges and immune *** incidence of TTP in Nanjing area was *** number of patients with TTP was 12 in 2019,6 in 2020,16 in 2021,and 19 in *** the authors’knowledge,this report is the first report of TTP associated with inactivated COVID-19 vaccine(CoronaVac).The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based *** plasma exchange is a vital treatment for CoronaVac-related TTP,similar to activated vaccine-related TTP.

关键词： thrombotic thrombocytopenia purpura(TTP) corona virus disease 2019(COVID-19) CoronaVac acute respiratory syndrome coronavirus 2(SARS-CoV-2) vaccine

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SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

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BIOCELL 2024年第3期48卷 453-462页

作者： JIYU WANG LIUYING YI KEKE HUANG YANGYANG WANG HUIPING WANG ZHIMIN ZHAI department of hematology The Second Affiliated Hospital of Anhui Medical UniversityHefei230601China department of hematology The Fourth Affiliated HospitalZhejiang University School of MedicineYiwu322000China

Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug ***,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic signiﬁcance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining speciﬁc inhibitors on apoptosis resistance in B-NHL-TIS ***:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of *** of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was *** doxorubicin(DOX)-inducible senescent B-NHL cells combined with the speciﬁc cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS *** expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were ***:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in *** of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and *** expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL ***:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.

关键词： SENEX B-cell non-Hodgkin lymphoma CDK4/6 G1-S phase transition Therapy-induced senescence Apoptosis resistance

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology hospital SuzhouChina department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu Yongping Song department of hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China department of hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin liang Wenbin Qian department of hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China department of hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China department of hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

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Oncology Research 2024年第4期32卷 753-768页

作者： QIAN HU MENGYAO WANG JINJIN WANG YALI TAO TING NIU department of hematology West China HospitalSichuan UniversityChengdu610041China

Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical *** study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated *** univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM *** comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression *** ARRS model emerged as an independent prognostic factor for predicting ***,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling ***,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this *** vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate *** employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and *** study presents compelling evidence establishing cell adhesion as a significant prognostic factor in ***,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such *** findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

关键词： Cell adhesion Bioinformatics Prognosis Multiple myeloma CAM-DR

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SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

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Current Medical Science 2024年第1期44卷 134-143页

作者： Yan-ni MA Yun-ding ZOU Zhi-long LIU Gui-xian WU Yuan-ze ZHOU Cheng-xin LUO Xiang-tao HUANG Ming-ling XIE Shuang-nian XU Xi LI department of hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China department of hematology the Third Affiliated Hospital(Daping Hospital)Third Military Medical University(Army Medical University)Chongqing 400042China

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 *** of SENP3 has been proven to be involved in the development of various ***,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains *** study was aimed to elucidate the effect of SENP3 in *** The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or *** cells with stable SENP3 knockdown were constructed using short hairpin *** proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow *** sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in *** SENP3 was upregulated in MCL patient samples and *** of SENP3 in MCL cells inhibited cell proliferation and promoted cell ***,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 ***,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse *** SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

关键词： mantle cell lymphoma SENP3 cell proliferation apoptosis

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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway

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Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia ZHAO Yan-na YU Xiao-ling YIN Li-ming department of hematology Tongde Hospital of Zhejiang ProvinceHangzhou310012China Institute of hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China

Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell *** AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow *** morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,*** protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western ***-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were *** of subcutaneous tumor tissue were observed after hematoxylin and eosin ***1 and GATA-1 expressions were detected by immunohistochemical *** The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor ti

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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