Experimental hematology最新文献_第2页

A new era of functional experimentation in human hematopoiesis and leukemia research 人类造血和白血病研究功能实验的新时代。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-01 DOI: 10.1016/j.exphem.2024.104652

Thomas Köhnke, Yang Feng, Ravindra Majeti

引用次数: 0

Brief report: Chronic murine schistosomiasis causes aberrant hemostasis.

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-29 DOI: 10.1016/j.exphem.2024.104689

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

{"title":"Brief report: Chronic murine schistosomiasis causes aberrant hemostasis.","authors":"Joanna H Greenman, Lucie Moss, Shinjini Chakraborty, Bradley J Whitehead, Johan Palmfedt, 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":"Schistosomiasis afflicts >250 million people worldwide, leading to an annual loss of >3 million disability-adjusted life years. Schistosoma mansoni 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 S. mansoni infection shows wide-ranging changes in hemostatic function which may have clinically relevant implications for populations in endemic regions.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104689"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CBX7 inhibitors affect H3K9 methyltransferase-regulated gene repression in leukemic cells.

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-28 DOI: 10.1016/j.exphem.2024.104691

Anne P de Groot, Huong Nguyen, Jacobine S Pouw, Ellen Weersing, Albertina Dethmers-Ausema, Gerald de Haan

{"title":"CBX7 inhibitors affect H3K9 methyltransferase-regulated gene repression in leukemic cells.","authors":"Anne P de Groot, Huong Nguyen, Jacobine S Pouw, Ellen Weersing, Albertina Dethmers-Ausema, Gerald de Haan","doi":"10.1016/j.exphem.2024.104691","DOIUrl":"10.1016/j.exphem.2024.104691","url":null,"abstract":"The epigenome of leukemic cells is dysregulated, and genes required for cell cycle arrest and differentiation may become repressed, which contributes to the accumulation of undifferentiated malignant blood cells. Here, we show that the Polycomb group protein CBX7 can interact with H3K9 methyltransferases EHMT1/2 and SETDB1. We aimed to assess whether combined interfering with these H3K9 methyltransferases and CBX7 could derepress target genes and thereby induce growth arrest of leukemic cells. We found that pharmacologic inhibition of CBX7 abolishes the interaction of CBX7 with EHMT1/2 and SETDB1 and subsequently reduces H3K9 methylation levels which reactivates target gene expression. Reversely, upon pharmacologic inhibition of H3K9 methyltransferases, CBX7 can take over gene repression. Finally, we found that combined inhibition of CBX7 and EHMT1/2 or SETDB1 had additive effects on reducing cell growth and inducing differentiation. However, we did not detect changes in epigenetic modifications, nor target gene derepression, after combination treatment. In contrast, CBX7 inhibitors alone did affect both Polycomb-associated H2Aub-mediated gene repression as well as H3K9 methyltransferase activity. Therefore, we suggest that CBX7 is a promising therapeutic target in leukemia, as its inhibition can reactivate Polycomb and H3K9 methyltransferase target gene expression.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104691"},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754804","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

Sex-stratified association of variants in the serotonin 1A receptor gene with acute crisis pain among African American patients with sickle cell disease.

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-28 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":"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 (HTR1A) on pain variability in SCD. Four variants (rs6449693, rs878567, rs6294, and rs10042486) in HTR1A 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 HTR1A 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 HTR1A 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.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104692"},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche.

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-28 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":"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.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104686"},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential impact of CD34+ cell dose for different age groups in allogeneic hematopoietic cell transplantation for acute leukemia: a machine learning–based discovery cd34+ 细胞剂量对不同年龄组急性白血病异基因造血细胞移植的不同影响：基于机器学习的发现。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-23 DOI: 10.1016/j.exphem.2024.104684

Yiyang Qu , Hamed Shourabizadeh , Aravind Subramanian , Dionne M. Aleman , Louis-Martin Rousseau , Arjun D. Law , Auro Viswabandya , Fotios V. Michelis

{"title":"Differential impact of CD34+ cell dose for different age groups in allogeneic hematopoietic cell transplantation for acute leukemia: a machine learning–based discovery","authors":"Yiyang Qu , Hamed Shourabizadeh , Aravind Subramanian , Dionne M. Aleman , Louis-Martin Rousseau , Arjun D. Law , Auro Viswabandya , Fotios V. Michelis","doi":"10.1016/j.exphem.2024.104684","DOIUrl":"10.1016/j.exphem.2024.104684","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (allo-HCT) presents a potentially curative treatment for hematologic malignancies yet carries associated risks and complications. Continuous research focuses on predicting outcomes and identifying risk factors. Notably, the influence of CD34+ cell dose on overall survival (OS) has been the subject of numerous studies yielding contradictory results. We developed machine learning (ML) models to predict allo-HCT outcomes and, through the application of SHapley Additive exPlanations (SHAP), an explainable artificial intelligence (XAI) technique enabled the identification of new and clinically relevant feature-outcome relationships. In particular, we identified a clear interaction between CD34+ cell dose of peripheral blood stem cell (PBSC) grafts and patient age at allo-HCT for patients with acute leukemia. Results of multivariable analysis validated the interaction effect: in young patients with acute leukemia (aged ≤45 years), low dose of CD34+ cells (<4.3 × 106 CD34+/kg) was associated with better OS against high dose (≥7 ×106 CD34+/kg) (hazard ratio [HR], 0.38; p = 0.019), while for older patients with acute leukemia (>45 years), low CD34+ cell dose (<3.8 ×106 CD34+/kg) was associated with worse OS against high dose (≥6.1 ×106 CD34+/kg) (HR, 1.58; p = 0.033). In conclusion, our findings suggest that tailoring CD34+ cell dose by patient age may benefit patients with acute leukemia undergoing allo-HCT, while XAI showcases excellent proficiency in revealing such interactions.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104684"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709054","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

Microbiome and Hemato-immune Aging. "微生物组与血液免疫衰老"。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-22 DOI: 10.1016/j.exphem.2024.104685

Alban Johansson, Nicole Pui-Yu Ho, Hitoshi Takizawa

引用次数: 0

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

引用次数: 0

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 : 2024-11-15 DOI: 10.1016/j.exphem.2024.104673

Anna Ericsson, David J Richard, Erik Wilker, David R Lancia, 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, 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":"Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin-oxygen (HbO2) 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 HbO2 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 HbO2 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.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104673"},"PeriodicalIF":2.5,"publicationDate":"2024-11-15","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural diversity and function of the granulocyte colony-stimulating factor in medaka fish. 青鳉体内粒细胞集落刺激因子的结构多样性与功能

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-14 DOI: 10.1016/j.exphem.2024.104672

Ayame Ogawa, Shungo Konno, Satoshi Ansai, Kiyoshi Naruse, Takashi Kato

{"title":"Structural diversity and function of the granulocyte colony-stimulating factor in medaka fish.","authors":"Ayame Ogawa, Shungo Konno, Satoshi Ansai, Kiyoshi Naruse, Takashi Kato","doi":"10.1016/j.exphem.2024.104672","DOIUrl":"10.1016/j.exphem.2024.104672","url":null,"abstract":"Diversity in the granulocyte repertoire, including neutrophils, basophils, and eosinophils, has been reported in vertebrate species. Medaka fish (Oryzias latipes) have only neutrophils; however, the storage pool of granulopoiesis tissues and the molecular mechanism of granulopoiesis in medaka fish have not been explored. Granulocyte colony-stimulating factor (G-CSF) is a cytokine responsible for neutrophil differentiation, survival, and proliferation. We performed in silico analysis to molecularly characterize the medaka G-CSF and G-CSF receptor (G-CSFR) genes. This study showed that medaka G-CSF differs considerably from human and mouse G-CSF in terms of the primary protein structure; however, the predicted tertiary structure was largely conserved. Analyses of lipopolysaccharide stimulation and G-CSF knockout and overexpression in medaka revealed that G-CSF mobilizes neutrophils into the peripheral blood. The analysis of G-CSF-deficient medaka revealed that G-CSF is involved in erythropoiesis. These findings represent an important first step toward understanding granulocyte hematopoiesis in nonmammalian species.","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104672"},"PeriodicalIF":2.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638408","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