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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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Waldenström macroglobulinemia:a challenging case treated with anti-CD19 CAR-T cell therapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 719-722页

作者： Yang YANG Xiaolin GU Jingsong HE Yongxian HU Zhen CAI Bone Marrow Transplantation Center Department of Hematologythe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China department of hematology Putuo People’s HospitalZhoushan 316100China

Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among *** significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell *** this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted *** anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.

关键词： CD19 globulin durability

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Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng Thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi department of Neurosurgery Heidelberg University HospitalHeidelbergGermany department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

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Defined hydrogels for spinal cord organoids:challenges and potential applications

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Neural Regeneration Research 2024年第11期19卷 2329-2330页

作者： Wai Hon Chooi Yuewen Wu Shi-Yan Ng Institute of Molecular and cell biology(IMCB) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore department of Physiology Yong Loo Lin School of MedicineNational University of Singapore(NUS)SingaporeSingapore

Organoids of the central nervous system,primarily derived from pluripotent stem cells or neural stem cells,are three-dimensional tissue cultures with self-organizing *** exposed to the right combinations of signals,they differentiate into a 3D tissue consisting of complex cytoarchitecture and native cell types,including various neuron subtypes and glial *** features closely mimic native tissues,making them invaluable for developmental studies and disease *** recent years,spinal cord organoids(SCOs)have been developed to investigate spinal cord development,injuries,and various neurological *** an integral part of the central nervous system,SCOs play a vital role and serve as a site for studying both neurodevelopment and neurodegenerative diseases.

关键词： properties injuries primarily

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EBV-associated lymphoproliferative disease post-CAR-T cell therapy

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Frontiers of Medicine 2024年第2期18卷 394-398页

作者： Shiyuan Zhang Xiaoxi Zhou Shangkun Zhang Na Wang Tongcun Zhang Donghua Zhang Qilin Ao Yang Cao Liang Huang department of hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan430030China Institute of biology and Medicine College of Life and Health SciencesWuhan University of Science and TechnologyWuhan430081China department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China 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 CollegeTianjin300020China Tianjin Institutes of Health Science Tianjin301600China

Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been *** patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of *** receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete ***,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting ***,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.

关键词： EBV-associated lymphoproliferative disease chimeric antigen receptor T-cell autologous stem cell transplantation immune checkpoint inhibitor

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RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key Laboratory of Molecular Design for Plant cell Factory of Guangdong Higher Education Institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell *** these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling ***,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely ***,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling ***1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its ***,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl *** darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome *** findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein

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Aldo-keto reductases:Role in cancer development and theranostics

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Oncology Research 2024年第8期32卷 1287-1308页

作者： SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY World Neem Organization Mumbai400101India department of Biochemistry ICMR-National Institute of NutritionHyderabad500007India department of Pathology and cell biology Columbia University Irving Medical CenterNew York10032USA

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various *** are aberrantly expressed in a wide range of malignant *** expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to *** have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and *** of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for *** classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical *** AKR inhibitors from natural sources also exhibit anticancer *** molecule inhibitors targeting speciﬁc AKR isoforms have shown promise in preclinical *** inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to *** this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug ***,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

关键词： Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors Cancer Drug-resistance Xenobiotics

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Regulation of aging by NELF-A and RNA polymerase Ⅱ elongation

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Neural Regeneration Research 2024年第7期19卷 1415-1416页

作者： Chin-Tong Ong Zhen-Kai Ngian Temasek Life Sciences Laboratory and department of Biological Sciences National University of SingaporeSingaporeSingapore department of Genetics Harvard Medical SchoolBostonMAUSA Institute of Molecular and cell biology Agency for ScienceTechnology and ResearchSingaporeSingapore

Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and *** in different animal models have l... 详细信息

关键词： aging twelve integrity

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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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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(pcell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(pcells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(Pcells 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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