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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

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

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

Recent advances and remaining challenges in lung cancer therapy

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Chinese Medical Journal 2024年第5期137卷 533-546页

作者： Tasha Barr Shoubao Ma Zhixin Li Jianhua Yu department of hematology and hematopoietic cell transplantation City of Hope National Medical CenterLos AngelesCalifornia 91010USA Comprehensive Cancer Center City of HopeLos AngelesCalifornia 91010USA department of Immuno-Oncology Beckman Research InstituteLos AngelesCalifornia 91010USA

Lung cancer remains the most common cause of cancer *** the continued research into new drugs and combination therapies,outcomes in lung cancer have been improved,and clinical benefits have been expanded to a broader patient ***,the overall cure and survival rates for lung cancer patients remain low,especially in metastatic *** the available lung cancer treatment options,such as surgery,radiation therapy,chemotherapy,targeted therapies,and alternative therapies,immunotherapy has shown to be the most *** exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer *** progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration(FDA)-approved drugs targeting the programmed cell death ligand-1 protein(e.g.,durvalumab,atezolizumab),the programmed cell death-1 receptor(e.g.,nivolumab,pembrolizumab),and cytotoxic T-lymphocyte-associated antigen 4(e.g.,tremelimumab,ipilimumab).Cytokines,cancer vaccines,adoptive T cell therapies,and Natural killer cell mono-and combinational therapies are rapidly being studied,yet to date,there are currently none that are FDA-approved for the treatment of lung *** this review,we discuss the current lung cancer therapies with an emphasis on immunotherapy,including the challenges for future research and clinical applications.

关键词： Lung cancer Therapy Immunotherapy Combination therapy Adoptive T cell therapies

Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome:A prospective multicenter clinical cohort study

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Chinese Medical Journal 2024年第9期137卷 1115-1117页

作者： Yigeng Cao Mingyang Wang Fuxu Wang Wenwen Guo Yueshen Ma Xiaoyun Li Yi He Aiming Pang Rongli Zhang Weihua Zhai Xin Chen Qiaoling Ma Jialin Wei Donglin Yang Yong Huang Dan Feng Jia Liu Xin Gao Shupeng Wen Wen Wang Tao Wang Ying Li Xiaosheng Fang Yingchun Li Xiaohan Zhang Yun Cai Yongqi Wang Weijie Cao Runqing Lu Sizhou Feng Rong Guo Yuewen Fu Xin Du Zhuogang Liu Xin Wang Ling Wang Liangming Ma Chuanfang Liu Xuejun Zhang Mingzhe Han Erlie Jiang department of hematopoietic stem cell transplantation Center State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Second Hospital of Hebei Medical UniversityHebei Key Laboratory of HematologyShijiazhuangHebei 050000China Center for Information and Resource State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China department of hematology Shanxi Bethune HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi 030032China department of hematology Qingdao Central HospitalUniversity of Health and Rehabilitation SciencesQingdaoShandong 266042China department of hematology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250000China department of hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China department of hematology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110000China department of hematology Shenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen University School of MedicineShenzhenGuangdong 518000China department of hematology Henan Cancer HospitalCancer Hospital Affiliated Zhengzhou UniversityZhengzhouHenan 450000China department of hematology Department of HematologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000China

To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are *** better conditioning regimens is urgently *** studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).

关键词： regimen myelo patients

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

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

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

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Science China Life Sciences 2024年

作者： Xiaodong Mo Weilong Zhang Guomei Fu Yingjun Chang Xiaohui Zhang Lanping Xu Yu Wang Chenhua Yan Mengzhu Shen Qiuxia Wei Changjian Yan Xiaojun Huang Peking University People's Hospital Peking University Institute of Hematology National Clinical Research Center for Hematologic Disease Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation department of hematology Lymphoma Research Center Peking University Third Hospital Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences

Measurable residual disease(MRD) is a powerful prognostic factor of relapse in acute myeloid leukemia(AML). We applied the single-cell RNA sequencing to bone marrow(BM) samples from patients with(n=20) and without(n=12) MRD after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+T cells enriched in the MRDnegative group(MRD-＿CD8), those enriched in the MRD-positive group(MRD+＿CD8) showed lower expression levels of cytotoxicity-related genes. Three monocyte clusters(i.e., MRD+＿M) and three B-cell clusters(i.e., MRD+＿B) were enriched in the MRD-positive group. Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-＿CD8 clusters and vice versa. MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-＿CD8 clusters. These findings revealed the characteristics of the immune cell landscape in MRD positivity, which will allow for a better understanding of the immune mechanisms for MRD conversion.

关键词：

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

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life Sciences) 2024年第8期67卷 1635-1647页

作者： Feng-Qi Liu Qing-Yuan Qu Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of hematopoietic stem cell transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of hematology Peking UniversityBeijing 100044China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow