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Immune cells in the B-cell lymphoma microenvironment:From basic research to clinical applications

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Chinese Medical Journal 2024年第7期137卷 776-790页

作者： Wenli Zhang Mengmeng Liu Wei Li Yongping Song Department of hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of hematology Henan Provincial Hematology HospitalZhengzhouHenan 450000China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical *** tumor microenvironment(TME)is a complex network in tumors,which consists of surrounding blood vessels,extracellular matrix,immune and non-immune cells,and signaling *** evidence has shown that the TME,especially immune cells within,is a double-edged sword,acting either as a tumor killer or as a promoter of tumor *** pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics,making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated ***,exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell *** this review,we elucidated the interaction between immune cells and tumor cells and their function in the initiation,progression,and prognosis of B-cell lymphoma,from preclinical experiments to clinical ***,we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

关键词： Tumor microenvironment B-cell lymphoma Immune cells Immunotherapy Targeted therapy

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

Treatment refractory mast cell leukemia with dominant gastrointestinal manifestation and concomitant skin symptoms:A case report

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World Journal of Clinical Cases 2024年第20期12卷 4317-4324页

作者： Maciej Tomasz Wysocki Maciej Gonciarz Bartosz Puła Department of Gastroenterology and Internal Medicine Military Institute of Medicine-National Research InstituteWarsaw 04-141Poland Department of hematology Institute of Hematology and Transfusion MedicineWarsaw 02-776Poland

BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor ***,tyrosine kinase inhibitors,and allogeneic hematopoietic cell transplantation are the only treatment options,but they cannot provide the desired outcomes in most cases of ***,other types of SM can be successfully *** disease has no specific manifestation,but gastroenterological symptoms are present in most *** SUMMARY The authors,hereby,report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of *** patient presented to the gastroenterology clinic with multiple,various,and unspecific gastroenterological *** of skin lesions significantly contributed to a relatively prompt *** serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast *** disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of *** Despite its“hematological nature”,MCL,in most cases presents dominantly with unspecific gastroenterological ***,a high disease awareness among physicians other than hematologists is necessary to improve treatment *** tryptase level,due to its non-invasive nature and easy access,may serve as an initial step to estimate the probability of mastocytosis.

关键词： Mastocytosis Systemic mastocytosis Mast cell leukemia Tryptase Case report

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU Department of hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China Department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

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 multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang Xiao-Li Ma Xiang-Ling He Wei-Hua Pan Xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Li Wei Yao Song Gu Wei-Ling Zhang Qiang Zhao Shi-Hao Huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen Huang Zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin Sun Xiao-Jun Yuan Department of Pediatric hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of hematology/Oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

Single-cell RNA sequencing reveals abnormal transcriptome signature of erythroid progenitors in pure red cell aplasia

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Genes & Diseases 2024年第1期11卷 49-52页

作者： Yumei Liu Haiyue Niu Jie Ren Zhiqin Wang Li Yan Limin Xing Zonghong Shao Rong Fu Zhigang Cai Huaquan Wang Department of hematology Tianjin Medical University General HospitalTianjin 300052China School of Basic Medical Sciences Tianjin Medical UniversityTianjin 300070China

Pure red cell aplasia(PRCA)is a bone marrow failure syndrome characterized by severe anemia,reticulocytopenia,selective reduction,and even the absence of bone marrow erythroid precursors,while leukocyte and platelet counts are normal.1 Acquired PRCA can be divided into primary and *** are mediated by immune *** in the quantity and dysfunction of committed erythroid progenitors(EPs),including burst forming uniterythroid(BFU-E)and colony forming unit-erythroid(CFU-E),may be the source of reduced erythropoiesis and needs to be elucidated.

关键词： progenitor anemia leukocyte

Frequency of the C677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

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Open Journal of Genetics 2024年第1期14卷 13-25页

作者： N’Guessan-Blao Rebecca Yapo Vincent Yayo-Ayé Mireille Adjambri Eusèbe Koné-Koné Fatoumata Sawadogo Duni hematology and General Biology unit Faculty of Pharmaceutical and Biological Sciences Department of Biological Sciences Felix Houphouet-Boigny University Abidjan Ivory Coast Laboratory of Biology and Medical research National Institute of Public Health (INSP) Abidjan Ivory Coast Molecular Biology unit Center for Diagnosis and Research on AIDS and Other Infectious Diseases (CeDReS) Treichville University Hospital (CHU) Abidjan Ivory Coast

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

关键词： Type 2 Diabetes C677T of MTHFR G20210A Factor V Leiden Thrombosis

Revolutionizing genetic disease treatment: The case of exagamglogene autotemcel

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The Innovation 2024年第3期5卷 5-6页

作者： Shuquan Rao Yao Yao Wenxuan Huo Yang Cao Lihua E.Budde State Key Laboratory of Experimental hematology Institute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020 China 2Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing 100044 China 3research unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences(2019RU029)Beijing 100044 China 4Department of hematology&Cancer Biology research Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030 China 5Department of hematology&Hematopoietic Stem Cell Transplantation City of Hope National Medical CenterDuarteCA 91010USA

Recent approval of exagamglogene autotemcel(exa-cel)on November 16,2023,in the united Kingdom,developed by Vertex Pharmaceuticals and CRISPR Therapeutics,represents the first cell-based therapy for treatment of sickle cell disease(SCD)with recurrent vaso-occlusive crises(VOCs)or transfusion-dependentβ-thalassemia(TDT)in patients aged 12 and *** suit,the US Food and Drug Administration authorized exa-cel for the same indications on December 8,***-cel represents the first commercially approved CRISPR-based gene therapy,offering hope to approximately 25,000 eligible patients in the US and *** significance of exa-cel extends beyond revolutionizing therapeutic intervention in genetic medicine;it also raises profound ethical considerations and societal implications related to genome manipulation.

关键词： transfusion treatment manipulation