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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 307-318页

作者： Lu Xu Zhi-Hao Xie Jun Li Shi Tao Fang-Li Ren Yin-Yin Wang Zhi-Jie Chang Xin-Bao Hao Department of hematology The First Affiliated Hospital of Hainan Medical UniversityHaikou570102China State Key laboratory of Membrane Biology School of MedicineTsinghua UniversityBeijing 100084China Heya Beijing Med-Biotech Inc. Beijing 100084China Department of hematology Roswell Park Comprehensive Cancer CenterNY 14263USA

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic ***:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival *** vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and ***:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor *** vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling ***:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular *** RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

关键词： RPRD1B RNAPⅡ Diffuse large B-cell lymphoma NF-κB Apoptosis

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

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Journal of Molecular Cell Biology 2024年第1期16卷 43-53页

作者： Xiaozhen Song Ruixing Hu Yi Chen Man Xiao Hong Zhang Shengnan Wu Qing Lu Molecular Diagnostic laboratory Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200040China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China laboratory of Development and Diseases and State Key laboratory for Medical Genomics Shanghai Institute of HematologyRuĳin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic *** mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental ***,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains *** this study,we employed zebrafish as an in vivo model ***7 knock down caused defects in zebrafish embryonic *** determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic ***,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of ***,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

关键词： TRAF7 coiled-coil domain crystal structure trimerization embryonic development

Mechanism and application of feedback loops formed by mechanotransduction and histone modifications

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Genes & Diseases 2024年第5期11卷 198-218页

作者： Han Sun Yafang Gao Xinyu Ma Yizhou Deng Lintao Bi Lisha Li Department of hematology and Oncology China-Japan Union HospitalJilin UniversityChangchunJilin 130021China The Key laboratory of Pathobiology Ministry of EducationCollege of Basic Medical SciencesJilin UniversityChangchunJilin 130021China

Mechanical stimulation is the key physical factor in cell *** acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specific signature alterations during the pathological *** research continues,the role of epigenetic science in mechanotransduction is attracting ***,the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been *** focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease ***,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling *** and epigenetic changes could be potential markers and therapeutic targets in clinical practice.

关键词： FAK Histone modifications MAPK Mechanotransduction RhoA WNT/b-catenin YAP/TAZ

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU Department of hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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

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

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

Not to be and how not to be:the questions of Tregs controlled by RIPK1

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Cellular & Molecular Immunology 2024年第2期21卷 205-206页

作者： Zhengcai Peng Huiyuan Zhang Hongbo Hu Center for Immunology and hematology Department of Biotherapy and Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Chongqing International Institute for Immunology Chongqing401338China

Millions of cells undergo daily cell death,a process essential for maintaining physiological homeostasis and *** forms of cell death,such as apoptosis,necroptosis,ferroptosis and pyroptosis,have been extensively studied for their distinct biological functions[1,2].Generally,programmed cell death,like apoptosis,is considered physiological and results in little to no inflammatory response.

关键词： death homeostasis pathogenesis

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key laboratory of Experimental hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

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Oncology Research 2024年第5期32卷 955-963页

作者： YAN ZHANG HEYANG ZHANG JING WANG XIN WEI YI QU FENG XU LIJUN ZHANG Department of hematology The First Affiliated Hospital of China Medical UniversityShenyang110001China

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among *** factor may play an important role in ***:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib *** expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM *** is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

关键词： Multiple Myeloma Peripheral neuropathy Bortezomib Bortezomib-induced peripheral neuropathy Next-generation sequencing MTHFR Serum Hcy