Experimental hematology最新文献_第4页

Patterns of hemolysis, erythropoiesis, and iron distribution define unique disease trajectories in three mouse models of genetic anemia 在三种遗传性贫血小鼠模型中，溶血、红细胞生成和铁分布的模式定义了独特的疾病轨迹。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-15 DOI: 10.1016/j.exphem.2025.104787

Irina L. Dubach, Raphael M. Buzzi, Dominik J. Schaer, Florence Vallelian

{"title":"Patterns of hemolysis, erythropoiesis, and iron distribution define unique disease trajectories in three mouse models of genetic anemia","authors":"Irina L. Dubach, Raphael M. Buzzi, Dominik J. Schaer, Florence Vallelian","doi":"10.1016/j.exphem.2025.104787","DOIUrl":"10.1016/j.exphem.2025.104787","url":null,"abstract":"<div><div>Hemolytic anemias involve premature red blood cell (RBC) destruction and present complex phenotypes, including disturbances in iron metabolism, extramedullary erythropoiesis, and systemic organ involvement. To guide the selection of appropriate <em>murine</em> models for studying pathophysiology and pharmacologic treatments of human hemolytic disorders, we systematically characterized three genetic mouse models commonly used to investigate such conditions: sickle cell disease (SCD), β-thalassemia (THAL), and hereditary spherocytosis (SPH). We sought to clarify how these models differ in the severity and nature of hemolysis, the balance between erythropoietic responses and iron regulation, and the long-term patterns of iron distribution. Our findings reveal that SPH mice exhibit severe intravascular hemolysis and suppressed hepcidin levels, leading to unopposed intestinal iron absorption and extensive tissue iron loading, especially in the liver. In contrast, SCD and THAL mice display predominantly extravascular hemolysis, moderate anemia, relatively stable hepcidin levels, and balanced erythropoiesis with partially regulated iron overload. Single-cell ribonucleic acid (RNA) sequencing of spleens highlighted distinct erythropoietic progenitor distributions, whereas iron-isotope tracing experiments confirmed divergent RBC turnover kinetics and tissue distribution. This study defines distinct disease trajectories for common hemolytic disease models by providing a unique comparative framework. Our work will support more informed model selection and refined experimental design to investigate hemolytic anemia pathobiology and therapeutics.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104787"},"PeriodicalIF":2.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Corrigendum to A novel lymphoid progenitor cell population (LSKlow) is restricted by p18INK4c Experimental Hematology Volume 44 Issue 9 (2016), 874-844.e5 一种新的淋巴祖细胞群（LSKlow）受到p18INK4c实验血液学卷44第9期（2016），874-844.e5的限制

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-05 DOI: 10.1016/j.exphem.2025.104770

Fang Dong , Sha Hao , Shihu Ma , Hui Cheng , Yajie Wang , Wen Zhou , Weiping Yuan , Hideo Ema , Tao Cheng

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Bcl7b and Bcl7c subunits of BAF chromatin remodeling complexes are largely dispensable for hematopoiesis BAF染色质重塑复合物的Bcl7b和Bcl7c亚基在造血中是必不可少的。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-03 DOI: 10.1016/j.exphem.2025.104769

Pierre Priam , Veneta Krasteva , Alexandre Polsinelli , Laurence Côté , Francis Dilauro , Thérèse-Marie Poinsignon , Pierre Thibault , Julie A. Lessard

{"title":"Bcl7b and Bcl7c subunits of BAF chromatin remodeling complexes are largely dispensable for hematopoiesis","authors":"Pierre Priam , Veneta Krasteva , Alexandre Polsinelli , Laurence Côté , Francis Dilauro , Thérèse-Marie Poinsignon , Pierre Thibault , Julie A. Lessard","doi":"10.1016/j.exphem.2025.104769","DOIUrl":"10.1016/j.exphem.2025.104769","url":null,"abstract":"<div><div>Chromatin remodelers have emerged as prominent regulators of hematopoietic cell development and potential drivers of various human hematological malignancies. ATP-dependent BAF chromatin remodeling complexes, related to yeast SWI/SNF, determine gene expression programs and consequently contribute to the self-renewal, commitment, and lineage-specific differentiation of hematopoietic stem cells (HSCs) and progenitors. Here, we investigated the elusive biological function of the core Bcl7b and Bcl7c subunits of BAF complexes in hematopoietic tissue. Our analysis of mouse constitutive knockout alleles revealed that both Bcl7b and Bcl7c are dispensable for animal survival and steady-state adult hematopoiesis. <em>Bcl7b</em> and <em>Bcl7c</em> double knockout (dKO) mice can maintain long-term hematopoiesis with no observable effect on the HSC compartment. Moreover, we show that <em>Bcl7b/Bcl7c</em> dKO HSCs are capable of normal multilineage hematopoietic reconstitution after competitive serial transplantation. Collectively, these studies suggest that the Bcl7b and Bcl7c subunits of BAF complexes are dispensable for normal hematopoiesis.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104769"},"PeriodicalIF":2.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-01 DOI: 10.1016/j.exphem.2025.104754

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Establishing a low-dose x-ray irradiation protocol for experimental acute graft-versus-host disease 建立实验性急性移植物抗宿主病的低剂量x射线照射方案。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-29 DOI: 10.1016/j.exphem.2025.104765

Michelle Klesse , Oliver Schanz , Annkristin Heine

{"title":"Establishing a low-dose x-ray irradiation protocol for experimental acute graft-versus-host disease","authors":"Michelle Klesse , Oliver Schanz , Annkristin Heine","doi":"10.1016/j.exphem.2025.104765","DOIUrl":"10.1016/j.exphem.2025.104765","url":null,"abstract":"<div><div>The investigation of graft-versus-host disease (GvHD) after allogeneic stem cell transplantation heavily relies on the use of experimental animal models and total body irradiation (TBI) as a conditioning regimen. However, <sup>137</sup>Cs is gradually being replaced as the main source of radiation due to safety concerns, and the transfer of established irradiation protocols to x-ray irradiators has proven difficult. Here, we describe the establishment of an x-ray–based irradiation protocol in an experimental mouse model for acute GvHD (C57BL6 → BALB/c). Our data show that commonly reported dosages of 6–9 Gy did not result in a viable model. Instead, irradiation with 5 Gy led to the development of clinical symptoms of GvHD in mice after transplantation with allogeneic bone marrow and T cells. Mice with GvHD displayed altered hemograms and increased serum levels of proinflammatory cytokines compared with mice without GvHD, which was accompanied by sequestration of donor lymphocytes within organs. Donor chimerism and hemogram analyses also indicated sufficient myeloablation and hematopoietic reconstitution. Overall, we show that low-dose x-ray TBI effectively promotes acute GvHD in a mismatched mouse model. We also propose that the transfer of previously established gamma-ray TBI protocols should be carefully evaluated according to individual circumstances.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104765"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Assessing the impact of cell isolation method on B cell gene expression using next-generation sequencing 利用下一代测序技术评估细胞分离方法对B细胞基因表达的影响。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-29 DOI: 10.1016/j.exphem.2025.104766

Amanda N. Henning, Jordan Pardoe, Darryl Owusu-Ansah, Hong Lei, Kobe Robichaux, Lara Perinet, Samantha Muccilli, Steven L. Highfill, Valeria De Giorgi

{"title":"Assessing the impact of cell isolation method on B cell gene expression using next-generation sequencing","authors":"Amanda N. Henning, Jordan Pardoe, Darryl Owusu-Ansah, Hong Lei, Kobe Robichaux, Lara Perinet, Samantha Muccilli, Steven L. Highfill, Valeria De Giorgi","doi":"10.1016/j.exphem.2025.104766","DOIUrl":"10.1016/j.exphem.2025.104766","url":null,"abstract":"<div><div>Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) is a widely explored research approach across multiple fields. Cell populations of interest are generally isolated before analysis, especially if low-frequency cell populations are desired. B cells, in particular, make up approximately 5%–10% of total PBMCs in healthy individuals, thus, isolation of B cell populations is crucial for researchers investigating B cell malignancies. The most widely used cell isolation methods include negative or positive magnetic cell sorting (MCS) and fluorescence-activated cell sorting (FACS). In contrast to negative MCS, it is widely believed that positive MCS and FACS may affect gene expression due to the direct interaction of cell selection antibodies with surface markers. To the best of our knowledge, no specific studies have examined these effects within CD19<sup>+</sup> B cell populations. To evaluate this, we have performed RNA sequencing (RNA-seq) on B cells isolated from four healthy donors using three distinct methods: positive and negative MCS using the EasySep StemCell Technologies kits and FACS, performed using the MACSQuant Tyto sorter (Miltenyi Biotec). We report significant gene expression changes following CD19-dependent B cell isolation via either positive MCS or FACS relative to negative MCS, including a general upregulation of genes associated with immune activity and receptor signaling and downregulation of RNA processing genes. These results suggest that B cell isolation methods should be taken into consideration when designing experiments or incorporating publicly available sequencing datasets into ongoing research studies, as they may significantly impact the reliability and interpretability of the findings.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104766"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Harnessing the potential of gene-editing technology to overcome the current bottlenecks of CAR-T cell therapy in T-cell malignancies 利用基因编辑技术的潜力，克服目前car-t细胞治疗t细胞恶性肿瘤的瓶颈。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-22 DOI: 10.1016/j.exphem.2025.104762

Ahmed H. Ismail , Mohsen A. Khormi , Wedad Mawkili , Amirah Albaqami , Sultan Areshi , Ali M. Aborasain , Maysa M. Hegazy , Ali H. Amin , Mabrouk A. Abo-Zaid

{"title":"Harnessing the potential of gene-editing technology to overcome the current bottlenecks of CAR-T cell therapy in T-cell malignancies","authors":"Ahmed H. Ismail , Mohsen A. Khormi , Wedad Mawkili , Amirah Albaqami , Sultan Areshi , Ali M. Aborasain , Maysa M. Hegazy , Ali H. Amin , Mabrouk A. Abo-Zaid","doi":"10.1016/j.exphem.2025.104762","DOIUrl":"10.1016/j.exphem.2025.104762","url":null,"abstract":"<div><div>T-cell malignancies (TCMs) include a diverse spectrum of hematologic cancers marked by complex biology and aggressive nature. Treating TCMs remains a critical unmet need in oncology with poor response to standard therapies. Chimeric antigen receptor (CAR)–T cell therapy is one of the most successful types of immunotherapy that has revolutionized cancer treatment, as evidenced by various approved products for CD19 B-cell malignancies and multiple myeloma. Nonetheless, due to some unique hurdles, such as the risk of CAR-T cell fratricide, product contamination with malignant cells, and severe T-cell aplasia, the translation of this treatment approach to TCMs has not been particularly successful. Moreover, irrespective of the type of treated cancer, CAR-T cell therapy can also present some complexities and potential side effects, such as cumbersome and costly manufacturing processes, impaired in vivo function, cytokine release syndrome (CRS), neurotoxicity, and leukemic transformation of CAR-T cells. Recent groundbreaking advances in gene-editing technology and the evolution of precise gene-editing tools such as the CRISPR/Cas9 system and its derivatives have opened a new way to overcoming the mentioned bottlenecks and paving the way for CAR-T cell therapy in TCMs. This review sheds light on how gene editing is being incorporated into CAR-T cell therapy to address current hurdles, enhance therapeutic efficacy, and improve the safety profile of CAR-T cell therapy in TCMs. Ongoing/conducted clinical trials are also discussed to provide a comprehensive view of the evolving landscape of genome-edited CAR-T cell therapy for TCMs.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104762"},"PeriodicalIF":2.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Special issue: bone marrow aging 特刊：骨髓老化。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-04 DOI: 10.1016/j.exphem.2025.104750

Anthony D. Ho , Atsushi Iwama

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IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-01 DOI: 10.1016/S0301-472X(25)00028-1

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D816V KIT mutation induces mitochondrial morphologic and functional changes through BNIP3 downregulation in human myeloid cell lines ROSA and TF-1 D816V KIT突变通过下调骨髓细胞系ROSA和TF-1的BNIP3诱导线粒体形态和功能改变。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-20 DOI: 10.1016/j.exphem.2025.104748

Sabina Cisa-Wieczorek , Maria Isabel Hernández-Alvarez , Matilde Parreño , Juan P. Muñoz , Elena Bussaglia , Maite Carricondo , Jose Ubeda , Patrice Dubreuil , Antonio Zorzano , Fabienne Brenet , Josep F. Nomdedeu

{"title":"D816V KIT mutation induces mitochondrial morphologic and functional changes through BNIP3 downregulation in human myeloid cell lines ROSA and TF-1","authors":"Sabina Cisa-Wieczorek , Maria Isabel Hernández-Alvarez , Matilde Parreño , Juan P. Muñoz , Elena Bussaglia , Maite Carricondo , Jose Ubeda , Patrice Dubreuil , Antonio Zorzano , Fabienne Brenet , Josep F. Nomdedeu","doi":"10.1016/j.exphem.2025.104748","DOIUrl":"10.1016/j.exphem.2025.104748","url":null,"abstract":"<div><div>The KIT receptor is a transmembrane protein found on the surface of many different cell types. Mutant forms of KIT are drivers of myeloid neoplasms, including systemic mastocytosis. The KIT D816V mutation is the most common, leading to constitutive activation of the receptor and its downstream targets, and it is highly resistant to c-KIT inhibitors. Metabolic rewiring is a common trait in cancer. We analyzed the metabolic profile induced by the KIT D816 mutation, measuring mitochondrial parameters in two myeloid cell lines. We found that the KIT D816V mutation causes a significant increase in mitochondrial abundance and activity associated with superoxide production, which could promote DNA instability. Functional and morphologic changes in mitochondria were associated with reduced levels of BNIP3 protein expression. We also detected low BNIP3 levels in clinical acute myeloid leukemia samples harboring D816V mutations. In addition, we have found constitutive mTOR activation in mutated cells, a pathway that has been shown to regulate autophagy. Our data suggest that KIT D816V increases mitochondrial activity through downregulation of BNIP3 expression, which increases mitochondrial number through the autophagy pathway. Alterations in the cellular metabolism induced by the KIT D816V mutation could be therapeutically exploited.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104748"},"PeriodicalIF":2.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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