Current Opinion in Hematology最新文献_第3页

Signaling mechanisms and cis -regulatory control of Samd14 in erythroid regeneration. Samd14在红系再生中的信号机制和顺式调控。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-07-01 Epub Date: 2025-04-24 DOI: 10.1097/MOH.0000000000000873

Kyle J Hewitt, Pooja Roy, Meg A Schaefer

{"title":"Signaling mechanisms and cis -regulatory control of Samd14 in erythroid regeneration.","authors":"Kyle J Hewitt, Pooja Roy, Meg A Schaefer","doi":"10.1097/MOH.0000000000000873","DOIUrl":"10.1097/MOH.0000000000000873","url":null,"abstract":"Purpose of review: This review evaluates the known mechanisms of regulating erythroid regeneration via the sterile alpha motif protein-14 ( Samd14 ) enhancer, Samd14's role in stem cell factor/Kit and erythropoietin (Epo) signaling, possible SAMD14 functions beyond erythropoiesis, and extrapolation to other anemia-response pathways.Recent findings: Samd14 expression is controlled by an anemia-activated E-box-GATA transcriptional enhancer required for erythroid regeneration, and the Samd14 protein is needed for acute anemia recovery. Samd14 interacts with actin capping proteins to elevate Kit signaling via MAPK and PI3K/Akt pathways in stress erythroid precursors and promotes Epo signaling at later stages. Whereas canonical cellular stress transcriptional mechanisms are involved in anemia (e.g. hypoxia-inducible HSF1, Nrf2, ATF4, and others), enhancers with sequence and molecular features resembling the Samd14 S14E cis -element - occupied by GATA1 and TAL1 - regulate anemia-activated proteins. Relative to physiological replacement of red blood cells, unique signaling cues are involved in erythroid regeneration at multiple stages.Summary: Anemia-activated proteins coordinate an acute increase in red blood cell production from erythroid progenitors to regenerate lost cells and restore homeostasis. The Samd14 locus provides an exemplary examination of cell signaling - through both stem cell factor/Kit and Epo as well as transcriptional mechanisms involved in erythroid regeneration.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"206-212"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Adenosine signaling in promoting the balance between erythropoiesis and myelopoiesis. 腺苷信号在促进红细胞生成和骨髓生成平衡中的作用。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-07-01 Epub Date: 2025-04-23 DOI: 10.1097/MOH.0000000000000872

Mahmoud Mikdar, Marion Serra, Slim Azouzi

{"title":"Adenosine signaling in promoting the balance between erythropoiesis and myelopoiesis.","authors":"Mahmoud Mikdar, Marion Serra, Slim Azouzi","doi":"10.1097/MOH.0000000000000872","DOIUrl":"10.1097/MOH.0000000000000872","url":null,"abstract":"Purpose of review: Adenosine signaling is emerging as a key regulator of hematopoietic lineage commitment, influencing both erythropoiesis and myelopoiesis. This review explores the distinct roles of adenosine receptors in balancing these processes, particularly under stress conditions. Since adenosine extracellular levels are increased in multiple hematological disorders, including sickle cell disease, deciphering the mechanisms downstream of adenosine receptor activation is crucial to understand the pathophysiology of these conditions.Recent findings: Extracellular adenosine levels in the bone marrow microenvironment are tightly regulated by CD39/CD73 activity and ENT1 uptake. Recent studies have shown that ENT1-mediated adenosine transport is crucial for adenosine intracellular metabolism and normal erythropoiesis, while increased extracellular adenosine levels impact hematopoietic differentiation through adenosine receptor activation. . High dose of exogenous adenosine inhibits erythroid proliferation by inducing G1 arrest and p53-mediated apoptosis. Furthermore, A 2B and A 3 receptor signaling inhibits erythroid differentiation, while adenosine signaling through A 3 also favors granulopoiesis.Summary: Collectively, these findings highlight adenosine signaling as a critical and multifaceted regulator of hematopoietic balance, offering novel insights into its therapeutic potential for managing disorders characterized by ineffective erythropoiesis and aberrant myelopoiesis.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"199-205"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Direct megakaryopoiesis. 直接megakaryopoiesis。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-07-01 Epub Date: 2025-04-21 DOI: 10.1097/MOH.0000000000000871

Hans-Willem Snoeck

{"title":"Direct megakaryopoiesis.","authors":"Hans-Willem Snoeck","doi":"10.1097/MOH.0000000000000871","DOIUrl":"10.1097/MOH.0000000000000871","url":null,"abstract":"Purpose of review: Megakaryocytes are large, polyploid cells that produce platelets and originate from hematopoietic stem cells (HSCs) in the bone marrow. While in the classical paradigm, megakaryocytes are generated in a stepwise fashion through increasingly committed progenitor stages, studies using in-vivo barcoding, transplantation, and in-vitro culture have suggested that, in addition, a more direct pathway existed. The relevance of this direct pathway and its functional and phenotypic characteristics were unclear, however.Recent findings: Recent publications using fate-mapping and single-cell transplantation now unequivocally demonstrate the existence of a direct megakaryocyte differentiation pathway, provide molecular characterization, and indicate distinct roles and regulation of both pathways. The direct pathway originates from a separate subset of 'top' HSCs, is enhanced by hematopoietic stress, inflammation and aging, bypasses multipotential progenitors, may be more active in myeloproliferative neoplasms, and generates phenotypically distinct megakaryocyte progenitors and more reactive platelets.Summary: Novel insights into the direct megakaryocyte differentiation pathway provide a deeper understanding of HSC biology, hematological recovery after myeloablation, and aging of the hematopoietic system, and suggest that this pathway may contribute to the increase in thrombotic incidents with age and in myeloproliferative neoplasms.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"213-220"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Platelets in vascular inflammation: fire-fighters or pyromaniacs? 血小板血管炎症：消防员还是纵火狂？

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-07-01 Epub Date: 2025-05-13 DOI: 10.1097/MOH.0000000000000877

Yacine Boulaftali, Steffen Massberg, Leo Nicolai

{"title":"Platelets in vascular inflammation: fire-fighters or pyromaniacs?","authors":"Yacine Boulaftali, Steffen Massberg, Leo Nicolai","doi":"10.1097/MOH.0000000000000877","DOIUrl":"10.1097/MOH.0000000000000877","url":null,"abstract":"Purpose of review: In this review, we aim to highlight recent insights into the mechanisms through which platelets contribute to vascular inflammation. We will discuss how platelets interact with other cellular players in the vascular milieu, their role in shaping inflammatory responses, and the potential therapeutic implications of targeting platelet function in inflammatory vascular diseases.Recent findings: Platelets are essential components in the processes of hemostasis and thrombosis. Their role is now widely acknowledged as far more complex than merely acting as \"band-aids\" or helping to \"clog a pipe\". Platelets are now recognized as crucial mediators in inflammatory reactions, particularly in various diseases of the vasculature, where they contribute to the onset and progression of injury. Through their interactions with leukocytes, vascular cells, and by supporting the coagulation cascade, platelets are able to finely regulate the extent and intensity of vascular damage.Summary: Recent findings underscore the remarkable diversity and functionality of platelets in vascular diseases. Mechanistic studies in preclinical models reveal promising therapeutic opportunities, which require further validation before being translated into clinical practice.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"221-230"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Gene therapy for sickle cell disease and thalassemia. 镰状细胞病和地中海贫血的基因治疗。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-02-27 DOI: 10.1097/MOH.0000000000000867

Natalia Scaramellini, Daniele Lello Panzieri, Maria Domenica Cappellini

{"title":"Gene therapy for sickle cell disease and thalassemia.","authors":"Natalia Scaramellini, Daniele Lello Panzieri, Maria Domenica Cappellini","doi":"10.1097/MOH.0000000000000867","DOIUrl":"10.1097/MOH.0000000000000867","url":null,"abstract":"Purpose of review: Thalassemia and sickle cell disease are among the most frequent monogenic hereditary diseases. Access to transfusions, iron chelation therapies and drugs such as hydroxyurea have improved life expectancy and quality of life. However, these diseases still cause significant disability. The first available curative therapy, bone marrow transplantation, is unfortunately not feasible for all patients. Over the past decade, numerous studies have focused on finding new curative therapies, and many clinical trials have evaluated different gene therapy approaches.Recent findings: The therapeutic targets focus on adding functional copies of the gene encoding β-globin in defective CD34 + cells, mainly using lentiviral vectors directed towards HSCs. More recently, the focus has shifted to inducing fetal hemoglobin production at therapeutic levels or repairing the underlying molecular defect, using novel gene editing techniques involving CRISPR-Cas9, transcription activation-like effector protein nucleases, zinc finger nucleases and base editing. Preclinical and clinical studies now focus on optimizing how gene therapy is performed and delivered to reduce or eliminate myeloablative treatment and its potential adverse events.Summary: In this review, we explore the potential to induce fetal hemoglobin production at therapeutic levels or to repair the underlying molecular defect that causes the disease genetically. Here, we review recent gene editing studies that are opening a new era in curative treatment for hemoglobinopathies.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"120-129"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

New mechanisms and therapeutic approaches to regulate vascular permeability in systemic inflammation. 调节全身炎症血管通透性的新机制和治疗方法。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-03-10 DOI: 10.1097/MOH.0000000000000864

Helen H Vu, Samantha A Moellmer, Owen J T McCarty, Cristina Puy

{"title":"New mechanisms and therapeutic approaches to regulate vascular permeability in systemic inflammation.","authors":"Helen H Vu, Samantha A Moellmer, Owen J T McCarty, Cristina Puy","doi":"10.1097/MOH.0000000000000864","DOIUrl":"10.1097/MOH.0000000000000864","url":null,"abstract":"Purpose of review: This review summarizes mechanisms that regulate endothelial vascular permeability in health and disease. In systemic inflammation, the endothelial barrier integrity is disrupted, which exacerbates vascular permeability, leading to organ failure and death. Herein we provide an overview of emerging therapeutic targets to reverse barrier dysfunction and preserve vascular permeability in inflammatory diseases like sepsis.Recent findings: Endothelial barrier function is regulated in part by the endothelial cell-specific protein, Roundabout 4 (ROBO4), and vascular endothelial (VE)-cadherin, a critical adherens junction protein, which act in concert to suppresses vascular permeability by stabilizing endothelial cell-cell interactions. We recently discovered a pathway by which activation of coagulation factor XI (FXI) enhances the cleavage of VE-cadherin by the metalloproteinase ADAM10, contributing to sepsis-related endothelial damage and loss of barrier function. Targeting FXI improved survival and reduced sVE-cadherin levels in a baboon model of sepsis while enhancing Robo4 expression decreased mortality in LPS-treated mice.Summary: Endothelial cell barrier dysfunction is a hallmark of excessive immune responses characteristic of systemic inflammatory diseases such as sepsis. Advances in understanding the molecular mechanisms regulating vascular permeability, for instance the newly discovered roles of FXI or ROBO4, may help identify novel therapeutic targets for mitigating vascular hyperpermeability in septic patients.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"130-137"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Red cells: not only hemoglobin - plasma membranes are also of paramount importance. 红细胞：不仅是血红蛋白，质膜也至关重要。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-03-27 DOI: 10.1097/MOH.0000000000000866

Anna Rita Migliaccio

引用次数: 0

The state of prediction models in hematologic disease: a worrisome assessment. 血液病预测模型的现状：令人担忧的评估。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-02-12 DOI: 10.1097/MOH.0000000000000865

Xichao Wang, Ke Zhang, Lei Wang, Jiaqi Xu, Yamin Wang, Suning Chen, Zaixiang Tang

{"title":"The state of prediction models in hematologic disease: a worrisome assessment.","authors":"Xichao Wang, Ke Zhang, Lei Wang, Jiaqi Xu, Yamin Wang, Suning Chen, Zaixiang Tang","doi":"10.1097/MOH.0000000000000865","DOIUrl":"10.1097/MOH.0000000000000865","url":null,"abstract":"Purpose of review: The lack of optimal treatments for haematological disorders has led to the need for prediction models for diagnosis, therapeutic decision-making and life planning. In this review, the worrying current state of predictive models in the field is discussed.Recent findings: Here, we reviewed 100 studies on prediction models in this field. Our analysis revealed a concerning state of affairs, with a prevalence of suboptimal research methodologies and questionable statistical practices. This includes insufficient sample sizes, inadequate model evaluations, lack of necessary reports of model results, etc. In this regard, we present statistical considerations in the development and validation process of numerous models. This will provide the reader with the statistical knowledge related to prediction model necessary to assess bias in studies, compare other published models and determine the clinical utility of models.Summary: Awareness among authors, reviewers and editors of the required statistical considerations is crucial. Reinforcing these in all studies involving prediction models is needed. We all should encourage their use in evaluating existing studies and taking them fully into account in future studies.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"176-185"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Editorial introductions. 编辑介绍。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-03-27 DOI: 10.1097/MOH.0000000000000869

引用次数: 0

The role of germline and somatic mutations in predicting cancer-associated thrombosis: a narrative review. 生殖系和体细胞突变在预测癌症相关血栓形成中的作用：一个叙述性的回顾。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-01-28 DOI: 10.1097/MOH.0000000000000861

Vincent Lanting, Merel Oskam, Hanneke Wilmink, Pieter W Kamphuisen, Nick van Es

{"title":"The role of germline and somatic mutations in predicting cancer-associated thrombosis: a narrative review.","authors":"Vincent Lanting, Merel Oskam, Hanneke Wilmink, Pieter W Kamphuisen, Nick van Es","doi":"10.1097/MOH.0000000000000861","DOIUrl":"10.1097/MOH.0000000000000861","url":null,"abstract":"Purpose of review: Patients with cancer have an increased risk of venous thromboembolism (VTE). Guidelines suggest to use risk assessment tools to guide decisions about thromboprophylaxis, but current tools have modest discriminatory ability. Genetic information from the germline or tumor has the potential to improve VTE prediction. Here, we provide a clinical overview of the current role of genetics in cancer-associated VTE.Recent findings: Germline mutations, such as factor V Leiden and prothrombin G20210A, are associated with a 2- to 2.5-fold increased VTE risk in patients with cancer. Tumor-specific somatic mutations also contribute to VTE risk, such as ALK rearrangements increasing the risk in nonsmall cell lung cancer and IDH1 mutations decreasing the risk in gliomas. Other somatic mutations associated with VTE independent of tumor type include KRAS , STK11 , MET , KEAP1 , CTNNB1 , and CDKN2B . Incorporating data on germline or somatic mutations in risk scores improves discriminatory ability compared with the Khorana score.Summary: Specific germline and somatic mutations are associated with an increased VTE risk in patients with cancer and potentially improve performance of clinical risk scores. The increasing and widespread use of genetic testing in cancer care provides an opportunity for further development of prediction models incorporating genetic predictors.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"138-145"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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