Current Opinion in Hematology最新文献_第6页

Pas de deux: the coordinated coupling of erythroid differentiation with the cell cycle. 双人舞：红细胞分化与细胞周期的协调耦合。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-16 DOI: 10.1097/MOH.0000000000000811

Merav Socolovsky

{"title":"Pas de deux: the coordinated coupling of erythroid differentiation with the cell cycle.","authors":"Merav Socolovsky","doi":"10.1097/MOH.0000000000000811","DOIUrl":"10.1097/MOH.0000000000000811","url":null,"abstract":"Purpose of review: Recent work reveals that cell cycle duration and structure are remodeled in lock-step with distinct stages of erythroid differentiation. These cell cycle features have regulatory roles in differentiation, beyond the generic function of increasing cell number.Recent findings: Developmental progression through the early erythroid progenitor stage (known as colony-forming-erythroid, or 'CFU-e') is characterized by gradual shortening of G1 phase of the cycle. This process culminates in a key transcriptional switch to erythroid terminal differentiation (ETD) that is synchronized with, and dependent on, S phase progression. Further, the CFU-e/ETD switch takes place during an unusually short S phase, part of an exceptionally short cell cycle that is characterized by globally fast replication fork speeds. Cell cycle and S phase speed can alter developmental events during erythroid differentiation, through pathways that are targeted by glucocorticoid and erythropoietin signaling during the erythroid stress response.Summary: There is close inter-dependence between cell cycle structure and duration, S phase and replication fork speeds, and erythroid differentiation stage. Further, modulation of cell cycle structure and speed cycle impacts developmental progression and cell fate decisions during erythroid differentiation. These pathways may offer novel mechanistic insights and potential therapeutic targets.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"96-103"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984617","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

Hematopoietic stem cell collection for sickle cell disease gene therapy. 用于镰状细胞病基因治疗的造血干细胞采集。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-09 DOI: 10.1097/MOH.0000000000000807

Alexis Leonard, Mitchell J Weiss

{"title":"Hematopoietic stem cell collection for sickle cell disease gene therapy.","authors":"Alexis Leonard, Mitchell J Weiss","doi":"10.1097/MOH.0000000000000807","DOIUrl":"10.1097/MOH.0000000000000807","url":null,"abstract":"Purpose of review: Gene therapy for sickle cell disease (SCD) is advancing rapidly, with two transformative products recently approved by the US Food and Drug Administration and numerous others under study. All current gene therapy protocols require ex vivo modification of autologous hematopoietic stem cells (HSCs). However, several SCD-related problems impair HSC collection, including a stressed and damaged bone marrow, potential cytotoxicity by the major therapeutic drug hydroxyurea, and inability to use granulocyte colony stimulating factor, which can precipitate severe vaso-occlusive events.Recent findings: Peripheral blood mobilization of HSCs using the CXCR4 antagonist plerixafor followed by apheresis collection was recently shown to be safe and effective for most SCD patients and is the current strategy for mobilizing HSCs. However, exceptionally large numbers of HSCs are required to manufacture an adequate cellular product, responses to plerixafor are variable, and most patients require multiple mobilization cycles, increasing the risk for adverse events. For some, gene therapy is prohibited by the failure to obtain adequate numbers of HSCs.Summary: Here we review the current knowledge on HSC collection from individuals with SCD and potential improvements that may enhance the safety, efficacy, and availability of gene therapy for this disorder.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"104-114"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742766","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

Macrocytic anemias. 巨红细胞性贫血

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-07 DOI: 10.1097/MOH.0000000000000804

Mark J Koury, Daniel J Hausrath

{"title":"Macrocytic anemias.","authors":"Mark J Koury, Daniel J Hausrath","doi":"10.1097/MOH.0000000000000804","DOIUrl":"10.1097/MOH.0000000000000804","url":null,"abstract":"Purpose of review: Over the last century, the diseases associated with macrocytic anemia have been changing with more patients currently having hematological diseases including malignancies and myelodysplastic syndrome. The intracellular mechanisms underlying the development of anemia with macrocytosis can help in understanding normal erythropoiesis. Adaptations to these diseases involving erythroid progenitor and precursor cells lead to production of fewer but larger red blood cells, and understanding these mechanisms can provide information for possible treatments.Recent findings: Both inherited and acquired bone marrow diseases involving primarily impaired or delayed erythroid cell division or secondary adaptions to basic erythroid cellular deficits that results in prolonged cell division frequently present with macrocytic anemia.Summary of findings: In marrow failure diseases, large accumulations of iron and heme in early stages of erythroid differentiation make cells in those stages especially susceptible to death, but the erythroid cells that can survive the early stages of terminal differentiation yield fewer but larger erythrocytes that are recognized clinically as macrocytic anemia. Other disorders that limit deoxynucleosides required for DNA synthesis affect a broader range of erythropoietic cells, but they also lead to macrocytic anemia. The source of macrocytosis in other diseases remains uncertain.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"82-88"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708522","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

microRNAs and thrombo-inflammation: relationship in sight. microRNAs与血栓-炎症：关系就在眼前。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-01-24 DOI: 10.1097/MOH.0000000000000803

Sonia Águila, Rocío González-Conejero, Constantino Martínez

引用次数: 0

Vascular microphysiological systems. 血管微生理系统

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-01-18 DOI: 10.1097/MOH.0000000000000802

Sarah E Shelton

{"title":"Vascular microphysiological systems.","authors":"Sarah E Shelton","doi":"10.1097/MOH.0000000000000802","DOIUrl":"10.1097/MOH.0000000000000802","url":null,"abstract":"Purpose of review: This review summarizes innovations in vascular microphysiological systems (MPS) and discusses the themes that have emerged from recent works.Recent findings: Vascular MPS are increasing in complexity and ability to replicate tissue. Many labs use vascular MPS to study transport phenomena such as analyzing endothelial barrier function. Beyond vascular permeability, these models are also being used for pharmacological studies, including drug distribution and toxicity modeling. In part, these studies are made possible due to exciting advances in organ-specific models. Inflammatory processes have also been modeled by incorporating immune cells, with the ability to explore both cell migration and function. Finally, as methods for generating vascular MPS flourish, many researchers have turned their attention to incorporating flow to more closely recapitulate in vivo conditions.Summary: These models represent many different types of tissue and disease states. Some devices have relatively simple geometry and few cell types, while others use complex, multicompartmental microfluidics and integrate several cell types and origins. These 3D models enable us to observe model evolution in real time and perform a plethora of functional assays not possible using traditional cell culture methods.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"155-161"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490848","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

Circulating endothelial cells in pathophysiology. 病理生理学中的循环内皮细胞

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-15 DOI: 10.1097/MOH.0000000000000814

Victor Emmanuel Brett, Francoise Dignat George, Chloe James

{"title":"Circulating endothelial cells in pathophysiology.","authors":"Victor Emmanuel Brett, Francoise Dignat George, Chloe James","doi":"10.1097/MOH.0000000000000814","DOIUrl":"10.1097/MOH.0000000000000814","url":null,"abstract":"Purpose of review: The purpose of this review is to synthesize recent insights into the roles and importance of circulating endothelial cells (CECs) as indicators of the severity, progression, and prognosis of vascular-related diseases.Recent findings: Recent studies have identified elevated counts of CECs in pathological conditions, notably inflammatory or cardiovascular diseases such as acute myocardial infarction and heart failure, underscoring their potential as sensitive indicators of disease. Furthermore, the rise in CEC levels in cancer patients, particularly with disease advancement, points to their role in cancer-associated angiogenesis and response to treatment.Summary: This review underscores the evolving significance of CECs as markers for evaluating the gravity and advancement of diseases with vascular injury, including cardiovascular diseases, cancer, inflammatory conditions, and thromboembolic events. These last years, efforts made to standardize flow cytometry detection of CEC and the development of highly sensitive techniques to isolate, quantify or phenotype rare cells open promising avenues for clinical application. This may yield extensive knowledge regarding the mechanisms by which endothelial cells contribute to a variety of vascular-related disorders and their clinical value as emerging biomarkers.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"148-154"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742764","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

Venous thromboembolism: diagnostic advances and unaddressed challenges in management. 静脉血栓栓塞症：诊断方面的进步和管理方面尚未解决的难题。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-12 DOI: 10.1097/MOH.0000000000000809

Rick Mathews, Monica T Hinds, Khanh P Nguyen

{"title":"Venous thromboembolism: diagnostic advances and unaddressed challenges in management.","authors":"Rick Mathews, Monica T Hinds, Khanh P Nguyen","doi":"10.1097/MOH.0000000000000809","DOIUrl":"10.1097/MOH.0000000000000809","url":null,"abstract":"Purpose of review: This review summarizes recent advances in developing targeted diagnostics for venous thromboembolism (VTE) and unaddressed knowledge gaps in patient management. Without addressing these critical data needs, the morbidity in VTE patients will persist.Recent findings: Recent studies investigating plasma protein profiles in VTE patients have identified key diagnostic targets to address the currently unmet need for low-cost, confirmatory, point-of-care VTE diagnostics. These studies and a growing body of evidence from animal model studies have revealed the importance of inflammatory and vascular pathology in driving VTE, which are currently unaddressed targets for VTE therapy. To enhance the translation of preclinical animal studies, clinical quantification of thrombus burden and comparative component analyses between modeled VTE and clinical VTE are necessary.Summary: Lead candidates from protein profiling of VTE patients' plasma offer a promising outlook in developing low cost, confirmatory, point-of-care testing for VTE. Additionally, addressing the critical knowledge gap of quantitatively measuring clinical thrombi will allow for an array of benefits in VTE management and informing the translatability of experimental therapeutics.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"122-129"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742767","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

Signaling networks guiding erythropoiesis. 引导红细胞生成的信号网络。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-07 DOI: 10.1097/MOH.0000000000000808

Shilpa Kuttikrishnan, Kirti S Prabhu, Abdul Q Khan, Shahab Uddin

引用次数: 0

Developmental regulation of primitive erythropoiesis. 原始红细胞生成的发育调节。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-27 DOI: 10.1097/MOH.0000000000000806

Marlies P Rossmann, James Palis

{"title":"Developmental regulation of primitive erythropoiesis.","authors":"Marlies P Rossmann, James Palis","doi":"10.1097/MOH.0000000000000806","DOIUrl":"10.1097/MOH.0000000000000806","url":null,"abstract":"Purpose of review: In this review, we present an overview of recent studies of primitive erythropoiesis, focusing on advances in deciphering its embryonic origin, defining species-specific differences in its developmental regulation, and better understanding the molecular and metabolic pathways involved in terminal differentiation.Recent findings: Single-cell transcriptomics combined with state-of-the-art lineage tracing approaches in unperturbed murine embryos have yielded new insights concerning the origin of the first (primitive) erythroid cells that arise from mesoderm-derived progenitors. Moreover, studies examining primitive erythropoiesis in rare early human embryo samples reveal an overall conservation of primitive erythroid ontogeny in mammals, albeit with some interesting differences such as localization of erythropoietin (EPO) production in the early embryo. Mechanistically, the repertoire of transcription factors that critically regulate primitive erythropoiesis has been expanded to include regulators of transcription elongation, as well as epigenetic modifiers such as the histone methyltransferase DOT1L. For the latter, noncanonical roles aside from enzymatic activity are being uncovered. Lastly, detailed surveys of the metabolic and proteomic landscape of primitive erythroid precursors reveal the activation of key metabolic pathways such as pentose phosphate pathway that are paralleled by a striking loss of mRNA translation machinery.Summary: The ability to interrogate single cells in vivo continues to yield new insights into the birth of the first essential organ system of the developing embryo. A comparison of the regulation of primitive and definitive erythropoiesis, as well as the interplay of the different layers of regulation - transcriptional, epigenetic, and metabolic - will be critical in achieving the goal of faithfully generating erythroid cells in vitro for therapeutic purposes.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"71-81"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984616","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

A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology. 血小板 C 型凝集素样受体-2 及其配体 podoplanin 在血管生物学中的作用。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-05-01 Epub Date: 2024-02-06 DOI: 10.1097/MOH.0000000000000805

Katsue Suzuki-Inoue, Nagaharu Tsukiji

{"title":"A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology.","authors":"Katsue Suzuki-Inoue, Nagaharu Tsukiji","doi":"10.1097/MOH.0000000000000805","DOIUrl":"10.1097/MOH.0000000000000805","url":null,"abstract":"Purpose of review: Platelets are essential for hemostasis and are also vital in lymphatic and lung development and the maintenance of vascular integrity. Platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) and its endogenous ligand podoplanin (PDPN) in lymphatic endothelial cells (LECs) and other cells regulate these processes. This review aims to comprehensively summarize the roles of platelet CLEC-2 and PDPN. This review also focuses on discussing the underlying mechanisms by which platelet CLEC-2 and PDPN mediate blood/lymphatic separation.Findings: CLEC-2/PDPN-induced platelet activation in the primary lymph sacs, developmental lymphovenous junctions, neonatal mesentery, and the site of tumor lymphangiogenesis prevents blood/lymphatic vessel misconnection. Further, CLEC-2/PDPN-induced platelet activation is essential for lung development. Mice deficient in CLEC-2 or PDPN show blood-filled lymphatics, lung malformations, and cerebrovascular abnormalities. CLEC-2 deletion in steady-state adult mice did not result in blood/lymphatic vessel mixing. In adulthood, CLEC-2 maintains vascular integrity and that of high endothelial venules in lymph nodes. CLEC-2 deletion in adulthood results in hemorrhage under inflammatory conditions, and hemolymph nodes.Summary: The platelet CLEC-2/LEC PDPN interaction prevents blood/lymphatic vessel mixing at active remodeling sites of the blood/lymphatic system, but not in steady-state adult mice. This interaction also regulates vascular integrity when vascular permeability increases before and after birth.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"130-139"},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742763","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