Experimental hematology最新文献_第3页

Chronic murine schistosomiasis causes aberrant hemostasis 摘要：慢性小鼠血吸虫病引起异常止血。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104689

Joanna H. Greenman , Lucie Moss , Shinjini Chakraborty , Bradley J. Whitehead , Johan Palmfeldt , Peter Nejsum , James P. Hewitson , Ian S. Hitchcock

{"title":"Chronic murine schistosomiasis causes aberrant hemostasis","authors":"Joanna H. Greenman , Lucie Moss , Shinjini Chakraborty , Bradley J. Whitehead , Johan Palmfeldt , Peter Nejsum , James P. Hewitson , Ian S. Hitchcock","doi":"10.1016/j.exphem.2024.104689","DOIUrl":"10.1016/j.exphem.2024.104689","url":null,"abstract":"<div><div>Schistosomiasis afflicts >250 million people worldwide, leading to an annual loss of >3 million disability-adjusted life years. <em>Schistosoma mansoni</em> causes intestinal schistosomiasis with parasite eggs either transversing intestinal tissue or lodging within the liver and other organs, causing intestinal hemorrhage and liver pathology. Large (∼1 cm) adult worms survive for years within blood vessels, but we lack a clear understanding of their impact on hemostasis. We used a chronic mouse model of schistosomiasis to determine the impact on platelet numbers, phenotype and function. Hemostatic function was assessed by platelet phenotyping (flow cytometry and proteomics), whole blood aggregometry, and longitudinal coagulometry. Although platelets from schistosome-infected mice lack elevated surface P-selectin and activated αIIbβ3, unbiased proteomic analysis reveals infection-induced increases in MHC-I, IgM and IgG antibodies, and complement components. Whole blood from schistosome-infected mice spontaneously aggregates in the absence of exogenous agonists. Conversely, prothrombin and activated partial thromboplastin times are prolonged at the chronic stage of infection (10–12 weeks). A mouse model of <em>S. mansoni</em> infection shows wide-ranging changes in hemostatic function which may have clinically relevant implications for populations in endemic regions.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104689"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767458","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

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/S0301-472X(25)00006-2

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Methodologic considerations on how to identify human hematopoietic stem cells

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-30 DOI: 10.1016/j.exphem.2025.104729

Taylor Hinchly , Dominique Bonnet , Fernando Anjos-Afonso

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TET2-loss enhances immediate and time-resolved interferon-γ signaling responses across myeloid differentiation TET2缺失会增强整个髓系分化过程中即时和时间分辨的 IFNγ 信号反应。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-22 DOI: 10.1016/j.exphem.2025.104727

Matthew T. Jenkins , Yunli E. Chu , Alana M. Franceski , Chad R. Potts , Rebecca Dubin , Kirsten M. Dickerson , Stanley C. Lee , Rui Lu , Robert S. Welner , P. Brent Ferrell

{"title":"TET2-loss enhances immediate and time-resolved interferon-γ signaling responses across myeloid differentiation","authors":"Matthew T. Jenkins , Yunli E. Chu , Alana M. Franceski , Chad R. Potts , Rebecca Dubin , Kirsten M. Dickerson , Stanley C. Lee , Rui Lu , Robert S. Welner , P. Brent Ferrell","doi":"10.1016/j.exphem.2025.104727","DOIUrl":"10.1016/j.exphem.2025.104727","url":null,"abstract":"<div><div>Signaling responses to cytokines are disrupted in clonal hematopoiesis and myeloid malignancies. To better identify specific signaling response alterations in the presence or absence of TET2, we developed a 36-parameter cytometry by time-of-flight (CyTOF) panel of both surface marker and phosphoprotein antigens in murine bone marrow (BM). We show diverse, cell-type specific inflammatory cytokine responses in healthy hematopoietic cells. We next investigated changes associated with BM cells from <em>Tet2<sup>KO</sup></em> mice. High-dimensional surface marker phenotyping revealed expansion of hematopoietic stem and progenitor cells (HSPCs), committed cKIT<sup>+</sup>Ly6C<sup>+</sup> myeloid progenitors, and monocytes. Loss of TET2 function increased the magnitude of response to extracellular perturbations, including interferon (IFN)γ and H<sub>2</sub>O<sub>2</sub>. Response time courses revealed that IFNγ-mediated pSTAT1 remains elevated over time in <em>Tet2<sup>KO</sup></em>. Further, IFNγ resulted in a more significant increase in major histocompatibility complex class II (MHCII) expression in <em>Tet2<sup>KO</sup></em> immortalized progenitor cells than in <em>Tet2<sup>WT</sup></em>. Inhibition of Janus kinase 1 and 2 (JAK1/2) with ruxolitinib significantly reduced STAT1 phosphorylation and MHCII expression in <em>Tet2<sup>KO</sup></em> cells. Our results identify targetable disrupted signaling responses in <em>Tet2<sup>KO</sup></em> cells.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104727"},"PeriodicalIF":2.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037740","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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A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells. 在kmt2a重排的儿童t细胞急性淋巴细胞白血病细胞中，一种独特的替代mRNA剪接谱鉴定了致癌CD44转录物变体3

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-09 DOI: 10.1016/j.exphem.2025.104712

Amanda Ramilo Amor, Sabina Enlund, Indranil Sinha, Qingfei Jiang, Ola Hermanson, Anna Nilsson, Shahrzad Shirazi Fard, Frida Holm

{"title":"A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells.","authors":"Amanda Ramilo Amor, Sabina Enlund, Indranil Sinha, Qingfei Jiang, Ola Hermanson, Anna Nilsson, Shahrzad Shirazi Fard, Frida Holm","doi":"10.1016/j.exphem.2025.104712","DOIUrl":"10.1016/j.exphem.2025.104712","url":null,"abstract":"<p><p>T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10-15% of all pediatric acute lymphoblastic leukemia (ALL) cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples, we have studied differences in gene and splice variant patterns in KMT2A-rearranged (KMT2A-r) T-ALL compared with KMT2A-negative (KMT2A-wt) T-ALL samples. Our results have identified a distinct gene expression and splice variant expression pattern in pediatric KMT2A-r patient samples including significant expression of splicing regulatory markers ESRP1 and MBNL3. Additionally, the prosurvival long transcript variant of BCL2 were upregulated in KMT2A-r compared with KMT2A-wt T-ALL samples. Lastly, increased levels of activating methylation in the promoter region of CD44 were identified followed by an upregulation of the oncogenic transcript variant CD44v3 in KMT2A-r T-ALL. Together, this suggests that CD44v3 could play a potential role as gene expression-based risk stratification of KMT2A-r T-ALL and could possibly serve as a therapeutic target using splicing modulators.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104712"},"PeriodicalIF":2.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964310","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

How age affects human hematopoietic stem and progenitor cells and the strategies to mitigate aging 年龄如何影响人类造血干细胞和祖细胞以及减轻造血干细胞老化的策略。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-07 DOI: 10.1016/j.exphem.2025.104711

Xueling Li , Jianwei Wang , Linping Hu , Tao Cheng

{"title":"How age affects human hematopoietic stem and progenitor cells and the strategies to mitigate aging","authors":"Xueling Li , Jianwei Wang , Linping Hu , Tao Cheng","doi":"10.1016/j.exphem.2025.104711","DOIUrl":"10.1016/j.exphem.2025.104711","url":null,"abstract":"<div><div>Hematopoietic stem cells (HSCs) are central to blood formation and play a pivotal role in hematopoietic and systemic aging. With aging, HSCs undergo significant functional changes, such as an increased stem cell pool, declined homing and reconstitution capacity, and skewed differentiation toward myeloid and megakaryocyte/platelet progenitors. These phenotypic alterations are likely due to the expansion of certain clones, known as clonal hematopoiesis (CH), which leads to disrupted hematopoietic homeostasis, including anemia, impaired immunity, higher risks of hematological malignancies, and even associations with cardiovascular disease, highlighting the broader impact of HSC aging on overall health. HSC aging is driven by a range of mechanisms involving both intrinsic and extrinsic factors, such as DNA damage accumulation, epigenetic remodeling, inflammaging and metabolic regulation. In this review, we summarize the updated understanding of age-related changes in hematopoietic stem and progenitor cells (HSPCs) and the mechanisms underlying the aging process in mammalian models, especially in human study. Additionally, we provide insights into potential therapeutic strategies to counteract aging process and enhance HSC regenerative capacity, which will support therapeutic interventions and promote healthy aging.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104711"},"PeriodicalIF":2.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946751","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

Serum NMR metabolomics in distinct subtypes of hematologic malignancies 血液恶性肿瘤不同亚型的血清核磁共振代谢组学研究。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-07 DOI: 10.1016/j.exphem.2025.104710

Ayse Zehra Gul , Sahabettin Selek , Somer Bekiroglu , Metin Demirel , Fatma Betul Cakir , Bulent Uyanik

{"title":"Serum NMR metabolomics in distinct subtypes of hematologic malignancies","authors":"Ayse Zehra Gul , Sahabettin Selek , Somer Bekiroglu , Metin Demirel , Fatma Betul Cakir , Bulent Uyanik","doi":"10.1016/j.exphem.2025.104710","DOIUrl":"10.1016/j.exphem.2025.104710","url":null,"abstract":"<div><div>Hematologic malignancies encompass a diverse array of subtypes, contributing to substantial heterogeneity that poses challenges in predicting clinical outcomes. Leveraging the capabilities of nuclear magnetic resonance holds substantial promise in the detection of serum biomarkers and individual metabolic alterations in patients. This study involved the analysis of the sera from patients with acute myeloid leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma to investigate the affected metabolites and their associated pathways. The quantitative one-dimensional (1D) 1H nuclear magnetic resonance method was employed to identify alterations. Metabolite annotations were validated using two-dimensional (2D) analyses. Discriminating chemometric models and receiver operating characteristic curves were created using the MetaboAnalyst platform. The findings revealed significant alterations in the serum levels of amino acid catabolism products, citrate cycle intermediates, and phospholipids. The acute myeloid leukemia group showed differences in glucogenic amino acids related to the glycolysis pathway, whereas the chronic lymphocytic leukemia and non-Hodgkin lymphoma groups displayed variances in fumarate and acetate levels linked to the citrate cycle pathway. In the leukemia groups, higher levels of products from the protein degradation pathway were observed. The biomarker panels for each malignancy group exhibited outstanding discrimination from controls. Healthy individuals differed distinctly from patients, indicating commonly observed metabolic adaptation patterns among frequent hematologic malignancies. The small cohort study using nuclear magnetic resonance metabolomics in various hematologic malignancy subtypes revealed significant changes in serum amino acid and protein degradation end-product levels, suggesting prolonged leukocyte lifespan and increased energy demand.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104710"},"PeriodicalIF":2.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946823","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

Human pluripotent stem cell–derived hematopoietic progenitors and mature cells 人多能干细胞衍生的造血祖细胞和成熟细胞。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-03 DOI: 10.1016/j.exphem.2025.104713

Christopher M. Sturgeon, Eirini P. Papapetrou, Shannon McKinney-Freeman

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The diagnostic and therapeutic potential of multiple myeloma–associated circular RNAs 多发性骨髓瘤相关环状rna的诊断和治疗潜力。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-03 DOI: 10.1016/j.exphem.2024.104709

Yue Zhao , Shaokun Wang , Shuang Fu, Xinxin Wang, Jihong Zhang, Fang Chen

{"title":"The diagnostic and therapeutic potential of multiple myeloma–associated circular RNAs","authors":"Yue Zhao , Shaokun Wang , Shuang Fu, Xinxin Wang, Jihong Zhang, Fang Chen","doi":"10.1016/j.exphem.2024.104709","DOIUrl":"10.1016/j.exphem.2024.104709","url":null,"abstract":"<div><div>Circular RNA (circRNA) was first discovered in viruses in 1974; they are primarily formed through back splicing, where a downstream splice donor is joined to an upstream splice acceptor, resulting in a closed circRNA transcript. Under normal conditions, most circRNAs are stably expressed; however, in pathological conditions, circRNAs can play critical roles in the disease process of multiple myeloma (MM) through mechanisms such as competing endogenous RNAs (ceRNAs), regulation of transcription and splicing, affecting protein expression and localization, and even direct encoding of peptides. In recent years, there has been increasing interest in the role of circRNAs in MM and their regulatory functions during the disease process. Numerous studies have revealed that circRNAs are involved in the pathogenesis and prognosis of MM, aiding in the identification of reliable prognostic markers and potential therapeutic targets. Therefore, this review summarizes the structural characteristics of circRNAs, and their regulatory roles in MM, and introduces the latest advancements in understanding the novel functions of circRNAs in MM.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104709"},"PeriodicalIF":2.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930953","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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FT-4202, a selective pyruvate kinase R activator for sickle cell disease 治疗镰状细胞病的选择性丙酮酸激酶 R 激活剂 FT-4202。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-01-01 DOI: 10.1016/j.exphem.2024.104673

Anna Ericsson , David J. Richard , Erik Wilker , David R. Lancia Jr. , Shawn Fessler , Paul Troccolo , Xiaozhang Zheng , Angela Toms , Christopher Dinsmore , Lili Yao , Frans A. Kuypers , Sandra Larkin , Douglas Marcotte , Keertik Fulzele , Maria Ribadeneira , Sylvie M. Guichard , Gary Marshall

{"title":"FT-4202, a selective pyruvate kinase R activator for sickle cell disease","authors":"Anna Ericsson , David J. Richard , Erik Wilker , David R. Lancia Jr. , Shawn Fessler , Paul Troccolo , Xiaozhang Zheng , Angela Toms , Christopher Dinsmore , Lili Yao , Frans A. Kuypers , Sandra Larkin , Douglas Marcotte , Keertik Fulzele , Maria Ribadeneira , Sylvie M. Guichard , Gary Marshall","doi":"10.1016/j.exphem.2024.104673","DOIUrl":"10.1016/j.exphem.2024.104673","url":null,"abstract":"<div><div>Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin–oxygen (HbO<sub>2</sub>) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased HbO<sub>2</sub> affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays. FT-4202, an allosteric PKR activator, stabilizes the tetrameric enzyme and increases PKR activity in human and mouse RBCs in vitro. Seven-day oral administration of FT-4202 in Berkeley SCD mice reduced 2,3-DPG, increased HbO<sub>2</sub> affinity, and reduced RBC sickling versus control. There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104673"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644307","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}

引用次数: 0