Experimental hematology最新文献_第7页

Advice for effective leadership and hitting the ground running as a new group leader 为新任小组组长提供有效领导和顺利开展工作的建议。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-20 DOI: 10.1016/j.exphem.2024.104674

Lev M. Kats , Charles E. de Bock

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Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia 阿伐曲波帕与标准免疫抑制疗法联合治疗重型再生障碍性贫血的有效性和安全性

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-05 DOI: 10.1016/j.exphem.2024.104670

Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao

{"title":"Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia","authors":"Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao","doi":"10.1016/j.exphem.2024.104670","DOIUrl":"10.1016/j.exphem.2024.104670","url":null,"abstract":"<div><div>Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate, but its hepatotoxicity is concerning. Avatrombopag (AVA), a small-molecule thrombopoietin-receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study assessed the efficacy and safety of AVA added to IST 42 SAA patients compared to a historical cohort of 84 patients receiving IST alone, using propensity score matching. The median age was 31.5 (6.0–67.0 years) years old in group A and 26 (16.0–45.0 years) years old in group B. At 3 months, group A showed higher complete response (CR) and overall response (OR) rates than group B (CR: 19.0% vs. 4.8%, <em>p</em> = 0.024; OR: 54.8% vs. 39.3%, <em>p</em> = 0.145). Higher CR and OR rates were also found at 6 months in group A than in group B (CR: 31.0% vs. 14.3%, <em>p</em> = 0.145; OR 71.4% vs. 51.2%, <em>p</em> = 0.048). In multivariate analysis of group A, a shorter interval from disease onset to antithymocyte globulin (ATG) treatment (≤6 months) (<em>p</em> = 0.005) predicted better responses rate at 6 months. Event-free survival was also improved in group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in patients with SAA while ensuring safety.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104670"},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes 研究骨髓衰竭和 MDS 易感综合征的可诱导多能干细胞模型。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-02 DOI: 10.1016/j.exphem.2024.104669

Sushree S. Sahoo , Majd Khiami , Marcin W. Wlodarski

{"title":"Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes","authors":"Sushree S. Sahoo , Majd Khiami , Marcin W. Wlodarski","doi":"10.1016/j.exphem.2024.104669","DOIUrl":"10.1016/j.exphem.2024.104669","url":null,"abstract":"<div><div>Induced pluripotent stem cells (iPSCs) have emerged as powerful tools for <em>in vitro</em> modeling of bone marrow failure (BMF) syndromes and hereditary conditions predisposing to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This review synthesizes recent advances in iPSC-based disease modeling for various inherited BMF/MDS disorders, including Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia as well as <em>GATA2, RUNX1, ETV6, ANKRD26, SAMD9, SAMD9L</em>, and <em>ADH5</em>/<em>ALDH2</em> syndromes. Although the majority of these iPSC lines are derived from patient cells, some are generated by introducing patient-specific mutations into healthy iPSC backgrounds, offering complementary approaches to disease modeling. The review highlights the ability of iPSCs to recapitulate key disease phenotypes, such as impaired hematopoietic differentiation, telomere dysfunction, and defects in DNA repair or ribosome biogenesis. We discuss how these models have enhanced our understanding of disease pathomechanisms, hematopoietic defects, and potential therapeutic approaches. Challenges in generating and maintaining disease-specific iPSCs are examined, particularly for disorders involving DNA repair. We emphasize the necessity of creating isogenic controls to elucidate genotype-phenotype relationships. Furthermore, we address limitations of current iPSC models, including genetic variability among iPSC clones derived from the same patient, and difficulties in achieving robust engraftment of iPSC-derived hematopoietic progenitor cells in mouse transplantation models. The review also explores future directions, including the potential of iPSC models for drug discovery and personalized medicine approaches. This review underscores the significance of iPSC technology in advancing our understanding of inherited hematopoietic disorders and its potential to inform novel therapeutic strategies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104669"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IFC Editorial Board 国际金融公司编辑委员会

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-24 DOI: 10.1016/S0301-472X(24)00522-8

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Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development 对淋巴细胞发育的细胞和分子驱动因素的认识不断发展。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-23 DOI: 10.1016/j.exphem.2024.104667

Vu L. Tran , Myriam L.R. Haltalli , Jingjing Li , Dawn S. Lin , Masayuki Yamashita , Shalin H. Naik , Ellen V. Rothenberg

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Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis 剪接差异：利用造血过程中转录组的复杂性。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-10 DOI: 10.1016/j.exphem.2024.104655

Hannah M. Maul-Newby, Stephanie Halene

{"title":"Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis","authors":"Hannah M. Maul-Newby, Stephanie Halene","doi":"10.1016/j.exphem.2024.104655","DOIUrl":"10.1016/j.exphem.2024.104655","url":null,"abstract":"<div><div>Alternative splicing has long been recognized as a powerful tool to expand the diversity of the transcriptome and the proteome. The study of hematopoiesis, from hematopoietic stem cell maintenance and differentiation into committed progenitors to maturation into functional blood cells, has led the field of stem cell research and cellular differentiation for decades. The importance of aberrant splicing due to mutations in <em>cis</em> has been exemplified in thalassemias, resulting from aberrant expression of β-globin. The simultaneous development of increasingly sophisticated technologies, in particular the combination of multicolor flow cytometric cell sorting with bulk and single-cell sequencing, has provided sophisticated insights into the complex regulation of the blood system. The recognition that mutations in key splicing factors drive myeloid malignancies, in particular myelodysplastic syndromes, has galvanized research into alternative splicing in hematopoiesis and its diseases.</div><div>In this review, we will update the audience on the exciting novel technologies, highlight alternative splicing events and their regulators with essential functions in hematopoiesis, and provide a high-level overview how splicing factor mutations contribute to hematologic malignancies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104655"},"PeriodicalIF":2.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406302","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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BST2 facilitates activation of hematopoietic stem cells through ERK signaling BST2 通过 ERK 信号促进造血干细胞的活化

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-02 DOI: 10.1016/j.exphem.2024.104653

Marcus A. Florez , Apoorva Thatavarty , Duy T. Le , Holly A. Hill , Youngjae Jeong , Brian M. Ho , Pawel Kus , Trisha K. Wathan , Bailee N. Kain , Shixia Huang , Dongsu Park , Katherine Y. King

{"title":"BST2 facilitates activation of hematopoietic stem cells through ERK signaling","authors":"Marcus A. Florez , Apoorva Thatavarty , Duy T. Le , Holly A. Hill , Youngjae Jeong , Brian M. Ho , Pawel Kus , Trisha K. Wathan , Bailee N. Kain , Shixia Huang , Dongsu Park , Katherine Y. King","doi":"10.1016/j.exphem.2024.104653","DOIUrl":"10.1016/j.exphem.2024.104653","url":null,"abstract":"<div><div>The proinflammatory cytokine interferon gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell-surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, because it is induced upon IFN stimulation and required for IFN-dependent HSC activation. To identify the mechanism by which BST2 promotes IFN-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knockout (KO) of BST2 in a murine model does not disrupt immune cell responses to IFN-inducing mycobacterial infection. Furthermore, intravital imaging studies indicate that BST2 KO does not disrupt localization of HSCs relative to endothelial or osteoblastic niches in the bone marrow. However, using imaging-based flow cytometry, we found that IFNγ treatment shifts the lipid raft polarity of wild-type (WT) but not <em>Bst2<sup>−/−</sup></em> hematopoietic stem and progenitor cells (HSPCs). Furthermore, RNAseq analysis, reverse-phase protein array and western blot analysis of HSPCs indicate that BST2 promotes ERK1/2 phosphorylation during IFNγ-mediated stress. Overall, we find that BST2 facilitates HSC division by promoting cell polarization and ERK activation, thus elucidating a key mechanism of IFN-dependent HSPC activation. These findings inform future approaches in the treatment of cancer and bone marrow failure.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104653"},"PeriodicalIF":2.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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IFC Editorial Board 国际金融公司编辑委员会

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-09-18 DOI: 10.1016/S0301-472X(24)00505-8

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The Pluripotent Path to Immunotherapy 多能免疫疗法之路

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-09-07 DOI: 10.1016/j.exphem.2024.104648

Mame P. Diop, Sjoukje J.C. van der Stegen

{"title":"The Pluripotent Path to Immunotherapy","authors":"Mame P. Diop, Sjoukje J.C. van der Stegen","doi":"10.1016/j.exphem.2024.104648","DOIUrl":"10.1016/j.exphem.2024.104648","url":null,"abstract":"<div><div>Adoptive cell therapy (ACT) enhances the patient's own immune cells’ ability to identify and eliminate cancer cells. Several immune cell types are currently being applied in autologous ACT, including T cells, natural killer (NK) cells, and macrophages. The cells’ inherent antitumor capacity can be used, or they can be targeted toward tumor-associated antigen through expression of a chimeric antigen receptor (CAR). Although CAR-based ACT has achieved great results in hematologic malignancies, the accessibility of ACT is limited by the autologous nature of the therapy. Induced pluripotent stem cells (iPSCs) hold the potential to address this challenge, because they can provide an unlimited source for the in vitro generation of immune cells. Various immune subsets have been generated from iPSC for application in ACT, including several T-cell subsets (αβT cells, mucosal-associated invariant T cells, invariant NKT [iNKT] cells, and γδT cells), as well as NK cells, macrophages, and neutrophils. iPSC-derived αβT, NK, and iNKT cells are currently being tested in phase I clinical trials. The ability to perform (multiplexed) gene editing at the iPSC level and subsequent differentiation into effector populations not only expands the arsenal of ACT but allows for development of ACT utilizing cell types which cannot be efficiently obtained from peripheral blood or engineered and expanded in vitro.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"139 ","pages":"Article 104648"},"PeriodicalIF":2.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282635","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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Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma 弥漫大B细胞淋巴瘤患者接受免疫化疗后，自噬功能下调与临床疗效不佳有关。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-09-05 DOI: 10.1016/j.exphem.2024.104638

Ya-Li Zhang , Meng-Xue Ma , Li-Na Xing , Jing-Nan Zhang , Xiao-Nan Guo , Shu-kai Qiao

{"title":"Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma","authors":"Ya-Li Zhang , Meng-Xue Ma , Li-Na Xing , Jing-Nan Zhang , Xiao-Nan Guo , Shu-kai Qiao","doi":"10.1016/j.exphem.2024.104638","DOIUrl":"10.1016/j.exphem.2024.104638","url":null,"abstract":"<div><div>This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL and patients with reactive lymphoproliferative disease (RLD) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in RLD patients compared with those with DLBCL, but the difference was not statistically significant (<em>p</em> > 0.05). p62 levels in DLBCL patients were significantly higher than those in RLD patients (<em>p</em> < 0.05). Beclin-1 expression was associated only with the Ann Arbor stage (<em>p</em> < 0.05), whereas p62 expression was associated with the Ann Arbor stage, IPI score, extranodal involvement, and Ki-67 index (<em>p</em> < 0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in DLBCL patients. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (<em>p</em> > 0.05). However, high p62 expression in DLBCL patients was associated with reduced 2-year PFS compared with that of patients with low p62 expression (<em>p</em> < 0.05); the 2-year OS was not affected (<em>p</em> > 0.05). Our results demonstrate that autophagic activity affects the prognosis of DLBCL patients; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of DLBCL patients.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"139 ","pages":"Article 104638"},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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