Experimental hematology最新文献_第3页

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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Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling. 体外模型显示，低水平的CKS1抑制通过AKT/Foxo1信号传导促进造血。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-29 DOI: 10.1016/j.exphem.2025.104768

Juliana Fabiani Miranda, Adam Rogerson, Megan Guthrie, Kimrun Kaur, Emma Apperley, Mary Catherine Dunne, Navin Shridokar, Anjum Khan, William Grey

{"title":"Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling.","authors":"Juliana Fabiani Miranda, Adam Rogerson, Megan Guthrie, Kimrun Kaur, Emma Apperley, Mary Catherine Dunne, Navin Shridokar, Anjum Khan, William Grey","doi":"10.1016/j.exphem.2025.104768","DOIUrl":"10.1016/j.exphem.2025.104768","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are rare cells residing at the top of the haematopoietic hierarchy capable of reconstituting all blood cell populations through their ability of self-renewal and differentiation. Their ability to maintain haematopoiesis can be majorly depleted by chemotherapeutic agents, leading to a long-term bone marrow injury. However, pre-clinical studies have focused on the acute effects of chemotherapy, leaving the lasting impact on healthy cells poorly understood. To study this, we combined rapid ex vivo models to study the long-term/late-stage effects of a cyclin-dependent kinase subunit 1 (CKS1) inhibitor. Inhibition of CKS1 has been shown to protect healthy HSCs from chemotherapy during acute myeloid leukaemia, and here we show a dose-dependent role of long-term CKS1 inhibition on haematopoiesis, either boosting B lymphopoiesis or ablating HSC proliferation capacity, dependent on the context. Mechanistically, low doses of the CKS1 inhibitor (CKS1i) affects AKT-Foxo1 signalling potentiating B-cell differentiation, but impairing HSC proliferation. These results reveal a novel role for CKS1 in boosting B lymphopoiesis and propose the use of rapid ex vivo models to investigate the long-term effects of chemotherapeutic treatments targeting HSCs with the potential of reducing late adverse effects.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104768"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751821","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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Bone marrow niches for hematopoietic stem cells in homeostasis and aging 造血干细胞在体内平衡和衰老中的骨髓壁龛。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-18 DOI: 10.1016/j.exphem.2025.104749

Taichi Nakatani, Takashi Nagasawa

{"title":"Bone marrow niches for hematopoietic stem cells in homeostasis and aging","authors":"Taichi Nakatani, Takashi Nagasawa","doi":"10.1016/j.exphem.2025.104749","DOIUrl":"10.1016/j.exphem.2025.104749","url":null,"abstract":"<div><div>Among various types of candidate cells, including osteoblasts and Nestin<sup>+</sup> periarteriolar cells, several lines of histological and genetic evidence have demonstrated that the single population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)–abundant reticular (CAR) cells, which overlap strongly with leptin receptor–expressing (LepR<sup>+</sup>) cells, is the major cellular component of niches for hematopoietic stem cells (HSCs) and hematopoiesis in the bone marrow (BM). Expression of p16, a marker for senescent cells, and interleukin (IL)-1β and γH2AX foci, a marker for DNA damage, were increased in CAR/LepR<sup>+</sup> cells and osteoblasts with age. However, the most striking phenotype of aging in the human BM is yellow marrow, which consists predominantly of adipocytes, causing the decreased volume of the principal site of hematopoiesis probably with the decreased numbers of HSCs in the total body. BM adipocytes are derived from CAR/LepR<sup>+</sup> cells and act as negative or positive regulators of HSCs during homeostasis and myelosuppressive condition. Therefore, a fundamental question is how a portion of BM CAR/LepR<sup>+</sup> cells differentiate into adipocytes during aging. Many rounds of inflammatory stress induced yellow marrow in mice. On the other hand, type H vessels found in the metaphysis and peripheral nerves running along the arteries were markedly reduced in the marrow of aged mice, which might affect HSCs and/or their niche cells. Understanding the cellular and molecular function of aged HSC niches could enable pharmacological regulation of niche functions to facilitate control of disease caused by BM aging.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104749"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467483","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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