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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

SENEX gene promotes cell proliferation by activating RB/E2F pathway in diffuse large B-cell lymphoma cells

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BIOCELL 2021年第4期45卷 933-942页

作者： JIYU WANG YING PAN YANG WAN ZHIXIANG WANYAN ZHITAO WANG QIANSHAN TAO zhimin zhai Department of Hematology The Second Hospital of Anhui Medical UniversityHefei230601China

The present study aimed to clarify the role of SENEX in malignant cell proliferation in diffuse large B-cell lymphoma(DLBCL).22 DLBCL patients(6 newly diagnosed cases,7 cases at complete remission,and 9 relapsed cases)were included in the *** results indicated that both SENEX gene and protein were significantly increased in peripheral blood mononuclear cells(PBMCs)and tumor cells of relapsed DLBCL patients,accompanied by overexpression of p21,p16,and phosphorylated retinoblastoma(Rb).Silencing the SENEX gene in a DLBCL cell line caused a significant decrease in cell proliferation and inhibited cell cycle progression in the G1 *** Rb and E2F1 were also decreased,and activation of the Rb/E2F1 pathway was obviously *** conclude,the SENEX gene promotes proliferation in PBMC and tumor cells of DLBCL patients by activating the Rb/E2F1 pathway,in a manner suggesting that increased SENEX expression affects the relapse of DLBCL and may serve as an important target for DLBCL therapy.

关键词： SENEX DLBCL Cell proliferation Rb E2F

CD34^(+)CD38^(-)subpopulation without CD123 and CD44 is responsible for LSC and correlated with imbalance of immune cell subsets in AML

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BIOCELL 2022年第1期46卷 159-169页

作者： QIANSHAN TAO QING ZHANG HUIPING WANG HAO XIAO MEI ZHOU LINLIN LIU HUI QIN JIYU WANG FURUN AN zhimin zhai YI DONG Department of Hematology The Second Hospital of Anhui Medical UniversityHematology Research CenterAnhui Medical UniversityHefei230601China

Acute myeloid leukemia(AML)is regarded as a stem cell ***,no one unique marker is expressed on leukemia stem cells(LSC)but not on leukemic blasts nor normal hematopoietic stem cells(HSC).CD34^(+)CD38^(-)with or without CD123 or CD44 subpopulations are immunophenotypically defined as putative LSC fractions in ***,markers that can be effectively and simply held responsible for the intrinsical heterogeneity of LSC is still *** the present study,we examined the frequency of three different LSC subtypes(CD34^(+)CD38^(-),CD34^(+)CD38^(-)CD123^(+),CD34^(+)CD38^(-)CD44^(+))in AML at *** then validated their prognostic significance on the relevance of spectral features for diagnostic stratification,immune status,induction therapy response,treatment effect maintenance,and long^(-)term *** our findings,high proportions of the above three different LSC subtypes were all significantly characterized with low complete remission(CR)rate,high relapse/refractory rate,poor overall survival(OS),frequent FLT3^(-)ITD mutation,the high level of regulatory T cells(Treg)and monocytic myeloid^(-)derived suppressor cells(M^(-)MDSC).However,there was no significant statistical difference in all kinds of other clinical performance among the three different LSC *** was demonstrated that CD34^(+)CD38^(-)subpopulation without CD123 and CD44 might be held responsible for LSC and correlated with an imbalance of immune cell subsets in AML.

关键词： Acute myeloid leukemia Leukemia stem cells CD123 CD44 Immune cell subsets

TAT、PIC、TM、t-PAIC四种分子标志物在弥散性血管内凝血早期诊断中的价值

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中国科学技术大学学报 2020年第4期50卷 474-478页

作者：蒋冬雪翟志敏安徽医科大学第二附属医院血液科安徽合肥230601

目的探讨分子标志物凝血酶-抗凝血酶复合物(thrombin-antithrombin complex,TAT)、血栓调节蛋白(thrombomdulin,TM)、纤溶酶-α2纤溶酶抑制剂复合物(α2-plamininhibitor-plasmin complex,PIC)、组织型纤溶酶原激活剂-抑制剂复合物(tissue plaminogen antivator inhibitor complex,t-PAIC)在弥散性血管内凝血(disseminated intrascular coagulation,DIC)中的早期诊断价值.方法纳入233例有出血倾向或血栓患者的临床病例资料,根据2017年版中国DIC诊断积分系统(CDSS),分为显性DIC组、前DIC组和非DIC组,采用新的自动化技术检测实验室指标,包括TAT、TM、PIC、t-PAIC,比较各组间实验室指标的差异,评估其在DIC早期诊断中的价值.结果在显性DIC患者中,TAT、TM、PIC水平显著高于非DIC患者,t-PAIC在两组中无统计学意义;在前DIC患者中,TAT、TM、PIC、t-PAIC水平显著高于非DIC患者;ROC曲线显示,TAT、TM、PIC及t-PAIC联合诊断曲线下面积为0.887,联合凝血酶原时间(prothomin time,PT)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、D-二聚体(D-dimer,D-D)可达最大曲线下面积为0.933.结论TAT、TM、PIC及t-PAIC联合检测可提高DIC早期诊断率,为临床早期干预和治疗提供最佳时机.

关键词：弥散性血管内凝血凝血酶-抗凝血酶复合物血栓调节蛋白纤溶酶-α2纤溶酶抑制剂复合物组织型纤溶酶原激活剂-抑制剂复合物

A Case of EBV-Associated Hemophagocytic Lymphohistiocytosis in Adult: Lessons from the Treatment Process

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Open Journal of Blood Diseases 2020年第2期10卷 48-54页

作者： Wanqiu Zhang Jiakui Zhang Qianshan Tao Qing Zhang Yinwei Li Fan Wu zhimin zhai Department of Hematology Hematological Research Center The Second Affiliated Hospital of Anhui Medical University Hefei China

Hemophagocytic lymphohistiocytosis (HLH), which was first described in 1939 by paediatricians Scott and Robb-Smith, is a life-threatening disease. HLH is characterized as cytokine release syndrome which is caused by excessive but non-malignant activation of macrophages and/or histiocytes in bone marrow and other reticuloendothelial systems. EBV-HLH is the most common type of infection-associated HLH, has a high mortality rate without prompt and effective treatment. A previous study showed that the one-year mortality rate of EBV-HLH patients is 75%. Here we report a case of EBV-associated hemophagocytic syndrome in adult, and the lessons from the treatment process. Through this case, we think that for EBV-related HLH, EBV-DNA should also be monitored in addition to hemophagocytosis-related indicators during treatment. In addition, DEP regimen may not be suitable for patients who have received at least partial response, because impaired immunological functioning may lead to EBV and hemophagocytic re-activity.

关键词： Hemophagocytic Lymphohistiocytosis EBV Infection

Myelodysplastic Syndrome Secondary to Multiple Myeloma: A Case Report and Literature Review

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Journal of Biosciences and Medicines 2021年第3期9卷 39-43页

作者： Wanqiu Zhang Qianshan Tao Yinwei Li Yin Pan Qing Zhang Fan Wu zhimin zhai Department of Hematology Hamatological Research Center The Second Affiliated Hospital of Anhui Medical University Hefei China

Background: With the prolongation of survival in recent years, the accumulation of toxic and side effects of therapeutic drugs and the concomitant drug-related adverse reactions were reported in recent years. However, myelodysplastic syndrome secondary to multiple myeloma is rare. Objective: To improve the understanding of myelodysplastic syndrome secondary to multiple myeloma. Methods: The clinical data of a patient with myelodysplastic syndrome secondary to multiple myeloma after treatment were analyzed, and the related literature was reviewed. Results: A 54-year-old male patient was diagnosed as multiple myeloma in February 2014. After three courses of first-line induction chemotherapy, he achieved complete remission and received two courses of consolidation treatment. After that, he continued to take thalidomide orally. The disease recurred 13 months after complete remission (CR) with 6q+ karyotype change in 37 months. 21q- karyotype change was found in 39 months. The patient was finally diagnosed as treatment-related secondary myelodysplastic syndrome. Due to the poor effect of chemotherapy, the disease continued to deteriorate. Conclusion: In the course of multiple drug treatment, clinicians should pay attention to the changes of molecular genetics and the treatment-related secondary tumor.

关键词： Multiple Myeloma Myelodysplastic Syndrome Karyotype Thalidomide

1990-2019年中国非霍奇金淋巴瘤疾病负担分析

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中国循证医学杂志 2023年第8期23卷 880-886页

作者：肖慧吴凡安福润翟志敏安徽医科大学第二附属医院血液内科合肥230601

目的分析1990—2019年中国非霍奇金淋巴瘤(NHL)疾病负担情况及发展变化趋势。方法利用2019全球疾病负担数据库,分析NHL发病率、死亡率、伤残调整寿命年(DALY)及其相应的年龄标化率的变化情况,通过Joinpoint软件进行回归分析,计算标化发... 详细信息

目的分析1990—2019年中国非霍奇金淋巴瘤(NHL)疾病负担情况及发展变化趋势。方法利用2019全球疾病负担数据库,分析NHL发病率、死亡率、伤残调整寿命年(DALY)及其相应的年龄标化率的变化情况,通过Joinpoint软件进行回归分析,计算标化发病率、标化死亡率、标化DALY率的年度变化百分比(APC)和平均年度变化百分比(AAPC)以反映疾病负担变化趋势,并与全球数据进行比较。结果1990—2019年期间,我国NHL的疾病负担总体呈现上升趋势,与2019年相比,中国NHL标化发病率、标化死亡率、标化DALY率分别增长了144.72%、27.17%、15.61%。其年均变化率分别为3.12%、0.80%、0.51%。NHL疾病负担存在性别及年龄差异,随着年龄的增长疾病负担上升,男性高于女性。结论1990—2019年中国NHL的疾病负担呈现上升趋势,随着诊断与治疗方案发展,近几年疾病负担有所下降,但仍高于全球水平。对其发病机制及治疗方案仍需加强研究,对高危人群积极采取干预,以降低NHL的疾病负担。

关键词：非霍奇金淋巴瘤疾病负担 Joinpoint回归伤残调整寿命年

Toxoplasmosis-Associated Secondary Hemophagocytic Syndrome: A Case Report and Literature Review

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Open Journal of Blood Diseases 2020年第3期10卷 61-70页

作者： Xiang Sun Jiakui Zhang Qianling Ye Fan Wu Yinwei Li Qianshan Tao Qing Zhang Weiwei Zhu Huiping Wang Jinli Zhu zhimin zhai Department of Hematology Hamatological Research Center The Second Affiliated Hospital of Anhui Medical University Hefei China

Background: Toxoplasmosis is an extremely rare disease that occurs in the hosts contact with cat and dog frequently. Most human acute infections go unnoticed in immunocompetent individuals, and gradually transformed into chronic infection. However, while host immunity significantly waned, the risk of reactivation of chronic toxoplasma infection is greatly increased. Reactivation of latent toxoplasmic infection often presents with fever, leukopenia, thrombocytopenia, neurological signs and pneumonia. However, for the non-specific clinical and biological signs and its fetal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. Case Presenation: We report a case hospitalized for a week history of cough, anorexia and fatigue with nasal bleeding for a day. After hospitalization, broad-spectrum antibiotherapy was started without a clear diagnosis of infection. Then the patient did a lot of investigations to search the cause of infection, but there were no positive findings. However, an unexpected discovery was detected from peripheral blood smears, shows 1 - 3 μm in diameter, scattered, short and bow lik

关键词： Toxoplasmosis Infection Reactivation Hemophagocytic Syndrome

CD19和CD27标记系统性红斑狼疮患者外周血B细胞的亚群分析

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安徽医科大学学报 2006年第2期41卷 189-192页

作者：王春淮徐建华翟志敏安徽医科大学第一附属医院风湿科合肥230022 安徽医科大学附属省立医院中心实验室合肥230001

目的研究系统性红斑狼疮(SLE)外周血中B淋巴细胞亚群的分化状态及其与体液免疫的关系。方法选择SLE患者32例,SLEDAI分为≥10分组和<10分组;健康献血者14例作为对照。采用流式细胞仪检测研究对象外周血中CD19+CD27-、CD19+CD27+和CD19+CD... 详细信息

目的研究系统性红斑狼疮(SLE)外周血中B淋巴细胞亚群的分化状态及其与体液免疫的关系。方法选择SLE患者32例,SLEDAI分为≥10分组和<10分组;健康献血者14例作为对照。采用流式细胞仪检测研究对象外周血中CD19+CD27-、CD19+CD27+和CD19+CD27++细胞,并分析各亚群比例、CD19平均荧光强度的差异和体液免疫的关系。结果两组SLE患者与正常对照相比,CD19平均荧光强度明显降低。SLEDAI≥10分组的CD19+CD27++细胞比率较正常对照明显升高。SLEDAI<10分组的CD19+CD27-细胞较正常对照明显升高,CD19+CD27+细胞明显降低。IgG与浆母细胞比率呈正相关。CD19+CD27++细胞比率在抗dsDNA抗体阳性组较阴性组明显升高。结论SLE患者外周血CD19+CD27+及CD19+CD27++亚群存在异常,可能与SLE患者体内的体液免疫异常有关,并在其中发挥重要作用。

关键词：红斑狼疮,系统性抗原,CD19 抗原,CD27 B淋巴细胞亚群自身抗体