Experimental hematology最新文献

Corrigendum to A novel lymphoid progenitor cell population (LSKlow) is restricted by p18INK4c Experimental Hematology Volume 44 Issue 9 (2016), 874-844.e5

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

引用次数: 0

Bcl7b and Bcl7c Subunits of BAF Chromatin Remodeling Complexes are Largely Dispensable for Hematopoiesis.

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":"https://doi.org/10.1016/j.exphem.2025.104769","url":null,"abstract":"<p><p>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 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. Bcl7b and Bcl7c double knockout (dKO) mice can maintain long-term hematopoiesis with no observable effect on the hematopoietic stem cell (HSC) compartment. Moreover, we show that Bcl7b/Bcl7c dKO HSCs are capable of normal multi-lineage hematopoietic reconstitution after competitive serial transplantation. Collectively, these studies suggest that the Bcl7b and Bcl7c subunits of BAF complexes are dispensable for normal hematopoiesis.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"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}

引用次数: 0

IFC Editorial Board

IF 2.5 4区医学

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

引用次数: 0

Establishing a low-dose x-ray irradiation protocol for experimental acute graft-versus-host disease

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}

引用次数: 0

Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling.

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":"https://doi.org/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 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) activates Foxo1 signalling potentiating B-cell differentiation, but impairing HSC proliferation. These results reveal a novel role for the SCF-CKS1 complex in boosting haematopoiesis 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}

引用次数: 0

Assessing the impact of cell isolation method on B cell gene expression using next-generation sequencing

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}

引用次数: 0

HARNESSING THE POTENTIAL OF GENE EDITING TECHNOLOGY TO OVERCOME THE CURRENT BOTTLENECKS OF CAR-T CELL THERAPY IN T-CELL MALIGNANCIES.

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-21 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":"https://doi.org/10.1016/j.exphem.2025.104762","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104762"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","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}

引用次数: 0

Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells.

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-03-12 DOI: 10.1016/j.exphem.2025.104752

Min Ding, Yu Lu, Quan-Kai Lei, Yun-Wen Zheng

{"title":"Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells.","authors":"Min Ding, Yu Lu, Quan-Kai Lei, Yun-Wen Zheng","doi":"10.1016/j.exphem.2025.104752","DOIUrl":"10.1016/j.exphem.2025.104752","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogens, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cells (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain HSCs for long-term survival. Thus, we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104752"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630286","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}

引用次数: 0

Special issue: bone marrow aging

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

引用次数: 0

IFC Editorial Board

IF 2.5 4区医学

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

引用次数: 0