Experimental hematology最新文献_第5页

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}

引用次数: 0

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}

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 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}

引用次数: 0

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

引用次数: 0

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

引用次数: 0

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}

引用次数: 0

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}

引用次数: 0

In Memoriam: Prof. Vittorio Rizzoli, The visionary who built experimental hematology in Italy 纪念：维托里奥·里佐利教授，在意大利建立血液学实验的梦想家

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-17 DOI: 10.1016/j.exphem.2025.104735

引用次数: 0

Preconditioning intervention prior to allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia 高危急性髓性白血病患者异基因造血干细胞移植前的预处理干预。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-12 DOI: 10.1016/j.exphem.2025.104746

Takayoshi Tachibana , Akihiko Izumi , Shota Arai , Takaaki Takeda , Natsuki Hirose , Yotaro Tamai , Shuku Sato , Chizuko Hashimoto , Katsumichi Fujimaki , Ryuji Ishii , Hirotaka Sakai , Etsuko Yamazaki , Yasuyuki Inoue , Masatsugu Tanaka , Hideaki Nakajima

{"title":"Preconditioning intervention prior to allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia","authors":"Takayoshi Tachibana , Akihiko Izumi , Shota Arai , Takaaki Takeda , Natsuki Hirose , Yotaro Tamai , Shuku Sato , Chizuko Hashimoto , Katsumichi Fujimaki , Ryuji Ishii , Hirotaka Sakai , Etsuko Yamazaki , Yasuyuki Inoue , Masatsugu Tanaka , Hideaki Nakajima","doi":"10.1016/j.exphem.2025.104746","DOIUrl":"10.1016/j.exphem.2025.104746","url":null,"abstract":"<div><div>The outcomes of patients with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HCT) remain poor despite many attempts at developing therapeutic strategies. Preconditioning interventions (PCIs) have been applied to patients with high-risk AML to reduce the disease burden before starting the conditioning regimen. A single-center retrospective study was performed to evaluate the safety and efficacy of PCI in allograft patients with high-risk AML. Thirty-three patients with a median age of 57 (16–70) years were included to the entire cohort. Among various PCI regimens, venetoclax plus azacitidine was administered to 12 patients. The median drug withdrawal day was 0 days (range, 0–12) for low-intensity PCIs and 12 days (range, 8–14) for high-intensity PCIs. With no grade 3 nonhematological adverse events during PCIs, the median blast fraction in the bone marrow before and after PCIs decreased from 12.4% to 2.1% (<em>p</em> = 0.001). Excluding three patients with early complication-related deaths, all 30 patients achieved engraftment within a median of 30 days. The overall survival, cumulative incidence of relapse, and nonrelapse mortality (NRM) rates at 2 years were 67.1%, 23.9%, and 8.8%, respectively. The cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) at 100 days and chronic GVHD at 2 years were 32.4% and 23.5%, respectively. PCI may be safe and effective in promoting engraftment and reducing the risk of disease relapse without increasing the risk of NRM. Further clinical trials are warranted to establish appropriate PCI strategies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104746"},"PeriodicalIF":2.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425392","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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Charting new paths in experimental hematology: Revitalizing the editorial board and upcoming initiatives 绘制实验血液学的新路径：振兴编辑委员会和即将推出的举措。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-11 DOI: 10.1016/j.exphem.2025.104745

Keisuke Ito

引用次数: 0