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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

PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

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Science China(Life Sciences) 2024年第9期67卷 2033-2035页

作者： Meihan Gong Ye Yuan Zhongye Dai Xuejiao Lv Jiacheng Su Dawei Huo Lin Niu Xu Chen Xudong Wu State Key Laboratory of Experimental hematology The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsKey Laboratory of Immune Microenvironment and Disease(Ministry of Education)Department of Cell BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China bone marrow transplantation center the First Affiliated HospitalZhejiang University School of MedicineLiangzhu LaboratoryInstitute of HematologyZhejiang UniversityHangzhou 311113China

Dear Editor,Polycomb group proteins,conserved epigenetic transcriptional repressors,are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al.,2017).The polycomb repressive complex 2(PRC2)catalyzes H3 lysine-27 trimethylation(H3K27me3)to establish a delicate balance with H3K4me3,forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

关键词： valent thereby subsequent

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Insights from TARGET-seq:Inflammation drives TP53-mediated clonal evolution

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The Innovation 2024年第2期5卷 7-8页

作者： Yeqian Zhao Wenxuan Huo Yue Liang Xiaodong Mo Shanshan Pei Yanmin Zhao bone marrow transplantation center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Institute of hematology Zhejiang UniversityHangzhou 311121China Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing 100044China

Approximately 10%–20%myeloproliferative neoplasms(MPNs)can progress into blast-phase MPNs,also termed secondary acute myeloid leukemias(sAMLs),presenting dismal *** exhibits a distinctive clinical and pathological profile compared to de novo AML,marked by a higher incidence of erythroid leukemias and reduced responsive to conventional chemotherapies,resulting in a median survival of approximately 6 ***53 alterations are prevalent adverse events in leukemic transformation(LT),occurring in around one-third of sAML subjects.

关键词： TP53 neoplasms alterations

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires

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Cancer Innovation 2024年第3期3卷 1-21页

作者： Yulin Xu Wei Shan Qian Luo Meng Zhang Dawei Huo Yijin Chen Honghu Li Yishan Ye Xiaohong Yu Yi Luo He Huang bone marrow transplantation center The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu Laboratory Zhejiang UniversityHangzhouChina Institute of hematology Zhejiang UniversityHangzhouChina Zhejiang Province Engineering Research center for Stem Cell and Immunity Therapy HangzhouChina School of Medicine Zhejiang UniversityHangzhouChina

Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast ***,approaches to obtain cancer-reactive TCR-T cells have been ***:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune *** steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized *** human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and *** fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 ***,human T cells were processed for TCRβ-chain(TRB)sequencing *** the repertoires had been constructed,features such as the fraction,diversity,and immune signature were ***:The results demonstrated an increase in diversity and clonality of T cells after *** preferential usage and features of TRBV,TRBJ,and the V–J combination were also *** stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 *** burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized ***:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T *** platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.

关键词： cancer-targeted T-cell receptor T(TCR-T)cells circulating hematopoietic stem and progenitor cells(HSPCs) humanized mouse model steady-state peripheral blood T-cell receptorβ-chain(TRB) three-dimensional culture

The non-canonical poly(A)polymerase FAM46C promotes erythropoiesis

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Journal of Genetics and Genomics 2024年第6期51卷 594-607页

作者： Ke Yang Tiangi Zhu Jiaying Yin Qiaoli Zhangg Jing Li Hong Fan Gajing Han Weiyin Xu Nan Liu Xiang Lv bone marrow transplantation center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Liangzhu Laboratory Zhejang UniversityHangzhouZhejang 311121China Institute of hematology Zhejiang UniversityHangzhouZhejiang 311121China The State Key Laboratory for Complex Severeand Rare DiseasesHaihe Laboratory of Cell EcosystemDepartment of PathophysiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Medical Epigenetics Research center Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

The post-transcriptional regulation of mRNA is a crucial component of gene *** disruption of this process has detrimental effects on the normal development and gives rise to various *** for novel post-transcriptional regulators and exploring their roles are essential for understanding development and *** a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell ***46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroidspecific *** demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent ***,we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox *** conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.

关键词： FAM46C TENT5C Poly(A)polymerase Erythroblasts Post-transcriptional regulation Erythroid-specific enhancer

Aptamer-Based Cell-Surface Profiling with Single-Cell Resolution Enables Precise Cancer Characterization

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CCS Chemistry 2024年第1期6卷 196-207页

作者： Liujun Xu Yawei Feng Tong Wang Shenhuan Li Kangli Xu Yue Sun Yi Luo Yishan Ye Yan Miao Yun Dong Zhenzhen Guo Qing Zhang Benshang Li He Huang Xue-Qiang Wang Liping Qiu Weihong Tan Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan 410082 The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of MedicineChinese Academy of SciencesHangzhouZhejiang 310022 Institute of Molecular Medicine Renji HospitalShanghai Jiao Tong University School of MedicineCollege of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240 bone marrow transplantation center The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003 Institute of hematology Zhejiang UniversityHangzhou 310003 department of hematology and Oncology Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200127

Molecular profiling of cell-surface proteins is a powerful strategy for precise cancer *** mass cytometry(MC)enables synchronous detection of over 40 cellular parameters,its full potential in disease classification is challenged by the limited types of recognition probes currently *** this work,we synthesize a panel of heavy isotopeconjugated aptamers to profile cancer-associated signatures on the surface of hematological malignancy(HM)*** on 15 molecular signatures,we performed cell-surface profiling that allowed the precise classification of 8 HM cell *** with machine-learning technology,this aptamer-based MC platform also achieved multiclass identification of HM subtypes in clinical sampleswith 100%accuracy in the training cohort and 80%accuracy in the test ***,we report an effective and practical strategy for precise cancer classification at the singlecell level,paving the way for its clinical use in the near future.

关键词： molecular profiling cancer diagnosis mass cytometry aptamers machine learning

Current situation and development of hematopoietic cell transplantation centers:A nationwide survey in China

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Chinese Medical Journal 2024年第13期137卷 1626-1628页

作者： Yi Fan Mimi Xu Yuqing Tu Yu Hu Qifa Liu Weili Zhao Xiaohui Zhang Zimin Sun Ting Niu Jianda Hu Juan Li Lin Liu Li Liu Sanbin Wang Sujun Gao Yongrong Lai Xianmin Song Zhenyu Li Jingbo Wang Zhongxing Jiang Yajing Xu Jinsong Yan Pengcheng He Jianmin Yang Jia Chen Yang Xu Xiaojun Huang Depei Wu On behalf of the National Clinical Research center for Hematologic Diseases(NCRCH)at Suzhou National Clinical Research center for Hematologic Diseases The First Affiliated Hospital of Soochow UniversityJiangsu Institute of HematologySuzhouJiangsu 215000China department of hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of hematology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510510China State Key Laboratory of Medical Genomics Shanghai Institute of HematologyNational Research Center for Translational MedicineShanghai Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghai 215200China department of hematology Peking University People’s HospitalPeking University Institute of HematologyPeking UniversityBeijing 100044China department of hematology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China department of hematology West China HospitalSichuan UniversityChengduSichuan 610041China department of hematology Fujian Medical University Union HospitalFuzhouFujian 350001China department of hematology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China department of hematology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China department of hematology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China department of hematology General Hospital of Kunming Military Region of the People’s Liberation Army(PLA)KunmingYunan 650100China department of hematology and Oncology Bethune First Hospital Of Jilin UniversityChangchunJilin 130021China department of hematology The First Affiliated Hospital of Guangxi Medical UniversityGuilinGuangxi 530021China department of hematology Shanghai General HospitalShanghai 201620China department of hematology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu 221004China department of hematology Aerospace Center HospitalBei

To the Editor:Hematopoietic cell transplantation(HCT)is a vital modality to cure severe hematological disorders.[1]Global or regional summarized data of HCT are annually reported by the Chinese Blood and marrow transplantation Registry Group(CBMTRG),European Society for Blood and marrow transplantation(EBMT)and center for International Blood and marrow Transplant Research(CIBMTR).It is shown that the number of transplants is continuously increasing,particularly in China in recent years.[2]Since the donor accessibility is significantly addressed by the well-established protocol of haplo-identical HCT(haplo-HCT).

关键词： Blood hematopoietic centers

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Will artificial intelligence widen the therapeutic gap between children and adults?

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Pediatric Investigation 2024年第1期8卷 1-6页

作者： Matthew Nagy Bryan Sisk Albert Lai Eric Kodish Cleveland Clinic Lerner College of Medicine Case Western Reserve UniversityClevelandOhioUSA department of Pediatrics Division of Hematology/OncologyWashington University School of MedicineSt.LouisMissouriUSA department of Medicine Bioethics Research CenterWashington University School of MedicineSt.LouisMissouriUSA Institute for Informatics Washington University School of MedicineSt.LouisMissouriUSA department of Pediatric hematology Oncology and Blood and marrow transplantation Cleveland Clinic Children’sClevelandOhioUSA

The impending rise of artificial intelligence(AI)-powered healthcare offers exciting hope for improved care and outcomes in children with serious illnesses.1 The historical precedent in healthcare,however,suggests that advancements in adult care do not necessarily result in proportional progress in *** disparity was first noted in the mid-20th century when tragedies that involved drugs with well-studied and known adult safety profiles,such as sulfonamide elixir and thalidomide,resulted in harm to children due to limited pediatric clinical trial inclusion.2 As a result,legislation in 1962 required drug companies to include package labels that restricted or dissuaded the use of medications in children that were not properly studied in this population.2 Subsequently,physicians became reluctant to prescribe many medications,and pharmaceutical companies had little incentive to enroll children in trials as an unfavorable result could negatively impact sales in the adult market,and a successful outcome would only marginally increase the market pool.3 This lack of access led *** Shirkey to describe children as"therapeutic orphans"in 1968.2 After more than half a century of legislation aimed at increasing pediatric representation in research and drug development(Figure 1),enrollment of children in clinical trials remains disproportionately low,4 with children included in as few as 12%of trials for diseases with a burden equal to,or greater in,the pediatric versus adult population.

关键词： companies Figure properly

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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University bone marrow transplantation center of the First Affiliated Hospital and department of Cell Biology Zhejiang University School of Medicine department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy