Experimental hematology最新文献_第3页

Sex-stratified association of variants in the serotonin 1A receptor gene with acute crisis pain among African American patients with sickle cell disease 5 -羟色胺1A受体基因变异与非裔美国人镰状细胞病患者急性危重性疼痛的性别分层关联

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104692

Nilanjana Sadhu , Ying He , Yavnika Kashyap , Giokdjen Ilktach , Michael A. Wang , Yingwei Yao , Diana J. Wilkie , Robert E. Molokie , Zaijie Jim Wang

{"title":"Sex-stratified association of variants in the serotonin 1A receptor gene with acute crisis pain among African American patients with sickle cell disease","authors":"Nilanjana Sadhu , Ying He , Yavnika Kashyap , Giokdjen Ilktach , Michael A. Wang , Yingwei Yao , Diana J. Wilkie , Robert E. Molokie , Zaijie Jim Wang","doi":"10.1016/j.exphem.2024.104692","DOIUrl":"10.1016/j.exphem.2024.104692","url":null,"abstract":"<div><div>Patients with sickle cell disease (SCD) experience pain in their daily lives. Both the acute and chronic pain phenotypes of this disease exhibit high variability, making pain management a challenge. The underlying reasons for the phenotypic variability are poorly understood. Given the importance of serotonergic neurotransmission in pain signaling, we aimed to explore the role of variants in the 5-HT1A receptor gene (<em>HTR1A</em>) on pain variability in SCD. Four variants (rs6449693, rs878567, rs6294, and rs10042486) in <em>HTR1A</em> were genotyped in a cohort of 131 African Americans with SCD. Acute and chronic pain were measured by the acute care utilization and the McGill Pain Questionnaire, respectively. Association analyses were performed for three genetic models (additive, dominant, and recessive). Three variants (rs6449693, rs6294, and rs10042486) in <em>HTR1A</em> showed significant association with crisis pain in both the additive and dominant models. Although the G allele of rs6449693 and the C allele of rs10042486 associated with lower acute crisis pain, the T allele of rs6294 associated with increased acute crisis pain. Sex-stratified analyses revealed that the associations of these three variants with acute pain were significant only in men, but not in women. Furthermore, the A allele rs878567 that did not reach statistical significance in the overall cohort showed a significant association with lower crisis pain in men. To our knowledge, as the first study to explore the role of <em>HTR1A</em> variants in sickle cell pain, we identified that four variants across the gene are associated with acute crisis pain in SCD in a sex-stratified manner.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104692"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767462","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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Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche 定量评估HSPCs和骨髓生态位生物物理特性随年龄变化的新技术。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104686

Anthony D. Ho , Motomu Tanaka

{"title":"Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche","authors":"Anthony D. Ho , Motomu Tanaka","doi":"10.1016/j.exphem.2024.104686","DOIUrl":"10.1016/j.exphem.2024.104686","url":null,"abstract":"<div><div>The present knowledge on hematopoietic stem and progenitor cell (HSPC) biology and aging is based largely on studies in mouse models. Although mouse models are invaluable, they are not without limitations for defining how physical properties of HSPCs and their niche change with age. The bone marrow (BM) niche is a complex, interactive environment with multiple cell types. The structure and organization of the BM niche, especially the extracellular matrix (ECM), change with age. Provided with recent advances in quantitative analytical techniques and in vitro niche models, we have developed novel tools to quantitatively assess the impact of specific biochemical and physical cues on homing, adhesion, and migration of HSPCs. Recent developments in in vitro niche models have also provided new insights into the interactions between HSPCs and their niche, particularly the role of matrix stiffness. Further research is needed to integrate physical biomarkers into comprehensive mathematical models of age-dependent HSPC-niche interactions. The key is to use mouse models in conjunction with direct analyses in in vitro niche models to achieve a more comprehensive understanding of age-dependent alterations in niche function and regulation.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104686"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754825","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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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}

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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

引用次数: 0