Current Opinion in Hematology最新文献

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Gene therapy for sickle cell disease and thalassemia.
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","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.
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","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.
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
{"title":"Red cells: not only hemoglobin - plasma membranes are also of paramount importance.","authors":"Anna Rita Migliaccio","doi":"10.1097/MOH.0000000000000866","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000866","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"32 3","pages":"109-110"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722550","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
The state of prediction models in hematologic disease: a worrisome assessment.
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","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.
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
{"title":"Editorial introductions.","authors":"","doi":"10.1097/MOH.0000000000000869","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000869","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"32 3","pages":"v"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722546","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
The role of germline and somatic mutations in predicting cancer-associated thrombosis: a narrative review.
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells. 内皮细胞代谢信号控制肺部炎症损伤和修复
IF 3.1 3区 医学
Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2024-10-25 DOI: 10.1097/MOH.0000000000000848
Seth Gould, Ansley Herron, Jonathan Davis, Mollie Phillips, Mrinmay Chakrabarti, Colin E Evans
{"title":"Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.","authors":"Seth Gould, Ansley Herron, Jonathan Davis, Mollie Phillips, Mrinmay Chakrabarti, Colin E Evans","doi":"10.1097/MOH.0000000000000848","DOIUrl":"10.1097/MOH.0000000000000848","url":null,"abstract":"<p><strong>Purpose of review: </strong>Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies. We also describe studies of metabolic interventions that aim to inhibit ALI/ARDS and/or promote post-sepsis vascular repair, including those that target endothelial cell metabolites, endothelial cell metabolic signaling pathways, and endothelial cell metabolism.</p><p><strong>Recent findings: </strong>Endothelial cells are integral to both the injury and repair phases of ALI/ARDS. During the injury phase of ALI/ARDS, lung endothelial cell survival decreases, and lung endothelial cell-to-endothelial cell (EC-EC) junctions are weakened. During the repair phase after sepsis-induced lung injury, lung endothelial cell proliferation and lung EC-EC junction reannealing occur. These crucial aspects of ALI/ARDS and post-sepsis vascular repair, that is, endothelial cell viability, growth, and junction integrity, are controlled by a myriad of metabolites and metabolic signaling pathways in endothelial cells.</p><p><strong>Summary: </strong>Metabolic signaling pathways in endothelial cells represent a novel class of putative targets for the prevention and treatment of sepsis-induced inflammatory lung injury. Therapies that target metabolic signaling in endothelial cells are currently being explored as potential treatments for sepsis-induced inflammatory lung injury.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"157-167"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513343","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
Scoring systems to predict thrombotic complications in solid tumor patients.
IF 3.1 3区 医学
Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-02-07 DOI: 10.1097/MOH.0000000000000862
Swati Sharma, Sumit Sahni, Silvio Antoniak
{"title":"Scoring systems to predict thrombotic complications in solid tumor patients.","authors":"Swati Sharma, Sumit Sahni, Silvio Antoniak","doi":"10.1097/MOH.0000000000000862","DOIUrl":"10.1097/MOH.0000000000000862","url":null,"abstract":"<p><strong>Purpose of review: </strong>To explore the use of large datasets in predicting and managing cancer-associated venous thromboembolism (CAT) by stratifying patients into risk groups. This includes evaluating current predictive models and identifying potential improvements to enhance clinical decision-making.</p><p><strong>Recent findings: </strong>Cancer patients are at an elevated risk of developing venous thromboembolism (VTE), which significantly impacts mortality and quality of life. Traditional approaches to risk assessment fail to account for the procoagulant changes associated with cancer, making individualized risk prediction a challenge. Current clinical guidelines as per ASCO recommend risk assessment before chemotherapy and endorse thromboprophylaxis as a standard preventive measure. Since any cancer population is highly heterogeneous in terms of VTE risk, predicting the risk of CAT is an oncological challenge. To address this, different predictive models have been developed to stratify patients by risk, enabling targeted thromboprophylaxis. However, these models vary in accuracy and utility. The present review discusses the pros and cons of these different models.</p><p><strong>Summary: </strong>The review examines existing CAT risk prediction models, highlighting their strengths, limitations, and diagnostic performance. It also identifies additional variables that could enhance these models to improve their effectiveness in guiding clinicians toward better risk stratification and treatment decisions for cancer patients.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"168-175"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383295","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
Histological differences among thrombi in thrombotic diseases.
IF 3.1 3区 医学
Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-02-07 DOI: 10.1097/MOH.0000000000000860
Atsushi Yamashita, Toshihiro Gi, Yuichiro Sato
{"title":"Histological differences among thrombi in thrombotic diseases.","authors":"Atsushi Yamashita, Toshihiro Gi, Yuichiro Sato","doi":"10.1097/MOH.0000000000000860","DOIUrl":"10.1097/MOH.0000000000000860","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to summarize the histological differences among thrombi in acute myocardial infarction, ischemic stroke, venous thromboembolism, and amniotic fluid embolism, a newly identified thrombosis.</p><p><strong>Recent findings: </strong>Acute coronary thrombi have a small size, are enriched in platelets and fibrin, and show the presence of fibrin and von Willebrand factor, but not collagen, at plaque rupture sites. Symptomatic deep vein thrombi are large and exhibit various phases of time-dependent histological changes. Cancer-associated venous thromboemboli contain invasive cancer cells that penetrate the vascular walls, and small cancer cell aggregates are observed within the thrombi. The thrombus composition in atherosclerotic and cardioembolic ischemic strokes varies from case to case, while the thrombi in cancer-associated ischemic stroke are rich in platelets and fibrin. A pathological study on amniotic fluid embolism identified uterine vein thrombi and massive platelet-rich microthrombi in the lungs.</p><p><strong>Summary: </strong>Atherothrombus formation is induced by plaque disruption and may occlude a narrow lumen within a short time. Venous thrombi may grow to a large size in a multistage or chronic manner. Cancer cells can directly contribute to venous thrombus formation. The thrombus formation in amniotic fluid embolism may explain the occurrence of consumptive coagulopathy and cardiopulmonary collapse.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"146-156"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061502","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
Red blood cell metabolism: a window on systems health towards clinical metabolomics.
IF 3.1 3区 医学
Current Opinion in Hematology Pub Date : 2025-05-01 Epub Date: 2025-03-13 DOI: 10.1097/MOH.0000000000000863
Angelo D'Alessandro
{"title":"Red blood cell metabolism: a window on systems health towards clinical metabolomics.","authors":"Angelo D'Alessandro","doi":"10.1097/MOH.0000000000000863","DOIUrl":"10.1097/MOH.0000000000000863","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review focuses on recent advances in the understanding of red blood cell (RBC) metabolism as a function of hypoxia and oxidant stress. In particular, we will focus on RBC metabolic alterations during storage in the blood bank, a medically relevant model of erythrocyte responses to energy and redox stress.</p><p><strong>Recent findings: </strong>Recent studies on over 13 000 healthy blood donors, as part of the Recipient Epidemiology and Donor Evaluation Study (REDS) III and IV-P RBC omics, and 525 diversity outbred mice have highlighted the impact on RBC metabolism of biological factors (age, BMI), genetics (sex, polymorphisms) and exposure (dietary, professional or recreational habits, drugs that are not grounds for blood donor deferral).</p><p><strong>Summary: </strong>We review RBC metabolism from basic biochemistry to storage biology, briefly discussing the impact of inborn errors of metabolism and genetic factors on RBC metabolism, as a window on systems metabolic health. Expanding on the concept of clinical chemistry towards clinical metabolomics, monitoring metabolism at scale in large populations (e.g., millions of blood donors) may thus provide insights into population health as a complementary tool to genetic screening and standard clinical measurements.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"111-119"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626923","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
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