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Embracing the age of artificial intelligence:paradigm shifts,opportunities,and challenges in the treatment of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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Science China(Life Sciences) 2024年第6期67卷 1302-1304页

作者： Zhuo-Yu An Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Collaborative Innovation Center of hematology Peking UniversityBeijing 100044China Beijing Key Laboratory of Hematopoietic stem cell transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China

Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an important medical development in treating hematological ***,the risk of acute graft-versus-host disease(a GVHD)severely limits its use.a GVHD is a sev... 详细信息

关键词： hematopoietic graft artificial

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2885-2900页

作者： Porkizhi Arjunan Durga Kathirvelu Gokulnath Mahalingam Ashish Kumar Goel Uday George Zacharaiah Alok Srivastava Srujan Marepally Center for stem cell Research(A unit of instem Bengaluru)Christian Medical College CampusBagayamVellore 632002Tamil NaduIndia Manipal academy for higher education Mangalore 576104KarnatakaIndia Department of hematology Christian Medical College&HospitalVellore 632004Tamil NaduIndia Department of Hepatology Christian Medical College&HospitalVellore 632004Tamil NaduIndia

Inherited genetic disorders of the liver pose a significant public health *** transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive *** overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable *** viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their *** a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and ***,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

关键词： Lipid nanoparticle Liver disorders Gene therapy Gene editing Nucleic acid delivery pDNA mRNA siRNA ASO Clinical trials

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

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Oncology Research 2024年第1期32卷 49-60页

作者： QIUQIANG CHEN XUEJUN GUO WENXUE MA Key Laboratory for Translational Medicine The First Affiliated HospitalHuzhou University School of MedicineHuzhou313000China Department of hematology Puyang Youtian General HospitalPuyang457001China Department of Medicine Moores Cancer CenterSanford Stem Cell InstituteUniversity of California San DiegoLa JollaSan Diego92093USA

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune ***47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer ***,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely *** comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell ***,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic *** review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting *** the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if ***,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment ***,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

关键词： CD47 Cancer immunotherapy CD47-targeted therapies Tumor microenvironment Macrophage Cancer cell Immune evasion Checkpoint inhibitors CAR T-cell therapy Cancer treatment outcomes

Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

Charting epimutation dynamics in human hematopoietic differentiation Xiaohuan Qina

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Blood Science 2024年第3期6卷 1-10页

作者： Jiayi Lu Peng Wu Chunyong Zhang Lei Shi Ping Zhu State Key Laboratory of Experimental hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemDepartment of Stem Cell and Regenerative MedicineInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjinChina

DNA methylation plays a critical role in hematopoietic *** is a stochastic variation in DNA methylation that induces epigenetic ***,the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain *** this study,we developed a Julia package called EpiMut that enabled rapid and accurate quantification of *** was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature *** showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid *** dynamics of epimutations were observed during the differentiation of each ***,we found that epimutation significantly enriched signals associated with lineage ***,epimutations in hematopoietic stem cells(HSCs)derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell *** together,our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis,thereby offering insights into hematopoietic regulation.

关键词： DNA methylation Epimutation Hematopoietic differentiation Hematopoietic stem cell

Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (PTEN) in sensitivity of acute myeloid leukemia to chemotherapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 700-710页

作者： Liming LIN Jingjing TAO Ying MENG Yichao GAN Xin HE Shu LI Jiawei ZHANG Feiqiong GAO Dijia XIN Luyao WANG Yili FAN Boxiao CHEN Zhimin LU Yang XU Department of hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated Hospital and Institute of Translational MedicineCancer CenterZhejiang University School of MedicineHangzhou 310029China Institute of Genetics Zhejiang UniversityHangzhou 310058China Division of Hematopoietic stem cell&Leukemia Research Beckman Research Institute of City of HopeDuarteCA 91010USA Department of hematology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most ***,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)***101 suppresses the proliferation of myeloid malignancy cells and primary AML *** induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 *** knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling *** inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell *** findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

关键词： Genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library Phosphatase and tensin homologous(PTEN) Rapamycin Acute myeloid leukemia(AML) Chemotherapy

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

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Current Medical Science 2024年第3期44卷 611-622页

作者： Ying CHEN Bi-xia LI Ting-ting NIU Shu-jun YANG Li-chao WU Le-huai SHI Duo-bing ZOU Ning-ning WU Li-xia SHENG Xiao YAN Gui-fang OUYANG Qi-tian MU Laboratory of stem cell transplantation The First Affiliated Hospital of Ningbo UniversityNingbo315300China Ningbo Clinical Research Center For Hematologic Malignancies Ningbo315300China Department of hematology The First Affiliated Hospital of Ningbo UniversityNingbo315300China School of Medicine Hangzhou City UniversityZhejiang UniversityHangzhou310000China Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province Ningbo315300China

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast *** studies have demonstrated that circular RNAs play a role in AML *** this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this *** Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also *** growth was assessed using the cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow ***,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA *** Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell *** pull-down and sequencing identified miR-652-3p as a target microRNA of circ_*** growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p *** suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML *** Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

关键词： acute myeloid leukemia circ_0012152 miR-652-3p SOX4 cell growth

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

Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen Chenhua Yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched