{"title":"Novel neutrophil biology insights underlying atypical chemokine receptor-1/Duffy antigen receptor of chemokines-associated neutropenia.","authors":"Johnson M Liu, Hongbo R Luo","doi":"10.1097/MOH.0000000000000834","DOIUrl":"10.1097/MOH.0000000000000834","url":null,"abstract":"<p><strong>Purpose of review: </strong>Atypical chemokine receptor-1 (ACKR1)/Duffy antigen receptor of chemokines (DARC)-associated neutropenia (ADAN; OMIM 611862), previously named benign ethnic neutropenia, and present in two-thirds of individuals identifying as Black in the USA, is associated with mild to moderate decreases in peripheral neutrophil counts that nevertheless do not lead to increased infections. Consequently, recent initiatives have sought to establish normal neutrophil count reference ranges for ADAN, considering it a normal variant rather than a clinical disorder requiring medical intervention.</p><p><strong>Recent findings: </strong>A limited number of studies elucidating the mechanism of neutropenia in ADAN has suggested that neutrophils may redistribute from peripheral blood to the tissues including the spleen: this might explain why ADAN is not associated with increased risks of infection since the total number of neutrophils in the body remains normal. In this review, we critically examine the research underlying the molecular basis of ADAN.</p><p><strong>Summary: </strong>Insights into the biology of neutrophils and their trafficking may inform the clinical interpretation of neutropenia in ADAN. The bulk of research suggests that ADAN does not lead to a diminished host defense as do other forms of neutropenia. However, ADAN may lead to increased proinflammatory signaling, with possible implications for senescence of the immune system and predisposition to autoimmunity and cancer.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753431","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}
{"title":"New insights of glycoprotein Ib-IX-V complex organization and glycoprotein Ibα in platelet biogenesis.","authors":"Lulu Huang, Bojing Shao","doi":"10.1097/MOH.0000000000000832","DOIUrl":"10.1097/MOH.0000000000000832","url":null,"abstract":"<p><strong>Purpose of review: </strong>Glycoprotein (GP) Ib-IX-V, a platelet surface receptor that plays a critical role in platelet adhesion and platelet-mediated immune responses, consists of GPIbα, GPIbβ, GPIX, and GPV in a stoichiometry of 2 : 4 : 2 : 1. Forming a complex is essential for GPIb-IX-V to function. GPIb-IX-V also plays an important role in platelet biogenesis by regulating the number and size of platelets. Yet how GPIb-IX-V regulates platelet biogenesis remains elusive. This review will summarize recent findings in the complex organization of GPIb-IX-V and its role in platelet biogenesis.</p><p><strong>Recent findings: </strong>Proteomics studies suggest that GPIbα, GPIbβ, GPIX, and GPV form the complex in a ratio of 1 : 2 : 1 : 1, which is supported by analysis of molecular weight of GPIb-IX-V and GPIb-IX and the structure of entire GPIb-IX-V. To activate platelets, GPIbα requires binding of CLEC-2 to trigger signals. Furthermore, disrupting the GPIbα anchorage to filamin A causes defects in platelet budding away from proplatelets leading to giant platelets and a low platelet count.</p><p><strong>Summary: </strong>New studies challenge the traditional model for the organization of GPIb-IX-V as a complex and indicate the role of GPIb-IX-V in platelet production. Those studies provide insights for GPIb-IX-V in the regulation of platelet activation and platelet biogenesis.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762778","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}
{"title":"Prophylactic red cell transfusions for sickle cell disease pregnancy: increased use of therapy could transform outcomes.","authors":"Sheinei Alan, Deva Sharma, Lydia H Pecker","doi":"10.1097/MOH.0000000000000837","DOIUrl":"10.1097/MOH.0000000000000837","url":null,"abstract":"<p><strong>Purpose of review: </strong>Pregnancy for people with sickle cell disease (SCD) is high risk with persistently high rates of severe maternal and fetal mortality and morbidity. Transfusion therapy is the best-studied treatment for SCD in pregnancy; hydroxyurea is not usually used because of teratogenicity concerns. In high-resource settings, red cell transfusions are likely underutilized, while in low-resource settings, they may be altogether unavailable.</p><p><strong>Recent findings: </strong>A randomized controlled trial and meta-analysis, two of the strongest forms of clinical research, show transfusion significantly reduces maternal and fetal death, painful crisis, thrombosis, and acute respiratory failure. Downstream benefits of treatment are less well measured and may include improving maternal anemia, reducing opioid exposure, and avoiding hospitalization, which presents risk for additional complications. Alloimmunization is a particular transfusion risk in SCD. However, many strategies can mitigate this risk. Accordingly, the American Society of Hematology classifies chronic transfusion in pregnancy as low risk.</p><p><strong>Summary: </strong>Given the low risk classification, lack of alternative therapies, dismal, stagnant pregnancy outcomes and the potential for profound treatment benefit, wider use of chronic transfusion therapy for SCD pregnancy is likely indicated. This review discusses the benefits and potential risks of prophylactic transfusions for SCD pregnancy. Use of chronic transfusions during pregnancy is indicated to help urgently transform outcomes.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037833","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}
Shobana Navaneethabalakrishnan, Xiuli An, Francesca Vinchi
{"title":"Heme- and iron-activated macrophages in sickle cell disease: an updated perspective.","authors":"Shobana Navaneethabalakrishnan, Xiuli An, Francesca Vinchi","doi":"10.1097/MOH.0000000000000836","DOIUrl":"10.1097/MOH.0000000000000836","url":null,"abstract":"<p><strong>Purpose of review: </strong>Sickle cell disease (SCD) is a hereditary blood disorder due to a single-point mutation in the β-globin gene. The ensuing hemoglobin has the tendency to polymerize upon deoxygenation, leading to the typical sickle shape of red blood cells. While the primary pathology of sickle cell disease is a direct consequence of altered red blood cells, emerging evidence highlights the central role of macrophages in mediating hemoglobin scavenging, perpetuating oxidative stress and inflammation, and causing endothelial dysfunction and tissue remodeling.</p><p><strong>Recent findings: </strong>Recent research uncovered the impact of heme and iron overload on macrophage polarization and functions in sickle cell disease, and its implication for chronic inflammation and tissue damage in vital organs such as the liver, spleen, lungs and kidneys. By providing a thorough understanding of the dynamic interactions between macrophages and various cellular components within the sickle cell disease milieu, these studies have laid the foundation for the identification of macrophage-related cellular and molecular mechanisms potentially targetable for therapeutic purposes to attenuate sickle complications.</p><p><strong>Summary: </strong>This review provides a current update about recent discoveries on heme/iron-activated macrophages in SCD, shedding light on their critical role in disease pathophysiology. Ultimately, it proposes avenues for future research aimed at addressing the relevance of these cells for other sickle complications and at targeting them to mitigate disease morbidity and improve patient outcomes.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762777","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}
{"title":"Viral infection after hematopoietic stem cell transplantation.","authors":"Per Ljungman","doi":"10.1097/MOH.0000000000000833","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000833","url":null,"abstract":"<p><strong>Purpose of review: </strong>Viral infections are important complications after allogeneic hematopoietic stem cell transplantation. New infections develop such as SARS-CoV-2 with the potential for severe consequences. In this review, newly published information regarding management of viral infections is discussed.</p><p><strong>Recent findings: </strong>Letermovir and maribavir are antiviral agents that have positively impacted the management of cytomegalovirus infections. These should today be included in treatment algorithms. The first antiviral cellular therapy for anti-CD20 refractory EBV-associated lymphoproliferative disease is now licensed and available. Vaccination as well as introduction of antiviral agents, mAbs and possibly the development of different viral strains have reduced mortality in COVID-19 in this patient population. Well designed studies have shown the improved immunogenicity of high-dose influenza vaccines. There is still an unmet medical need for patients infected with human metapneumovirus and parainfluenza viruses.</p><p><strong>Summary: </strong>Although improvements in patient management for several important posttransplantation viral infections have been reported, an unmet medical need still exists for other viruses occurring in this high-risk population.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332724","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}
{"title":"Unrelated hematopoietic stem cell donor registries: present reality and future prospects.","authors":"Alexander H Schmidt","doi":"10.1097/MOH.0000000000000835","DOIUrl":"10.1097/MOH.0000000000000835","url":null,"abstract":"<p><strong>Purpose of review: </strong>Stem cell donor registries play an important role in providing stem cell products from unrelated donors to patients with severe blood diseases. In this review, important aspects of donor registry work, current challenges and possible future developments are discussed.</p><p><strong>Recent findings: </strong>The current growth in global unrelated stem cell donations is in line with the long-term trend, indicating that donor registries have overcome the COVID-19 pandemic. A key challenge for donor registries is the recruitment of donors from disadvantaged populations to create greater equity in access to unrelated stem cell transplantation. In addition, recruiting young donors and increasing the availability of donors who are already registered are important goals. In recent years, numerous studies have looked at the context of these themes and the development of possible solutions.</p><p><strong>Summary: </strong>The international community of donor registries, together with the World Marrow Donor Association, has helped many patients in need of a stem cell transplant over the past decades and is, therefore, a bright example of international collaboration for a good cause. It is currently addressing a number of challenges to effectively help as many patients as possible from various populations also in the future.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762779","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}
{"title":"Donor selection in allogeneic stem cell transplantation.","authors":"Francisco Barriga, Alberto Cardoso Martins Lima","doi":"10.1097/MOH.0000000000000831","DOIUrl":"10.1097/MOH.0000000000000831","url":null,"abstract":"<p><strong>Purpose of review: </strong>Recent progress in human leukocyte antigen (HLA) characterization, increased accrual of unrelated donors and cord blood units, and a new platform for haploidentical transplantation have resulted in the widespread availability of donors for allogeneic hematopoietic stem cell transplantation.</p><p><strong>Recent findings: </strong>Advances in HLA typing have identified an increasing number of loci and alleles that are crucial for successful transplantation. Newer HLA A, B, C, DRB1, and DQB1 alleles, DPB1 mismatches, and HLA B leader sequence matching are incorporated into donor selection algorithms. Donor selection is highly relevant because of recently published conflicting studies using different donor types. These studies are largely retrospective and compare patients with different diseases and stages, conditioning regimens, graft versus host disease (GVHD) prophylaxis, and time periods. A broad consensus indicates that the best donor is an available matched sibling, followed by a matched unrelated donor, and then alternative donors such as haploidentical, mismatched unrelated, and cord blood units. This consensus is being challenged by other factors, such as donor age, patient condition, urgency of transplantation, and costs involved.</p><p><strong>Summary: </strong>In this review, we will analyze the unique characteristics of each donor type, the HLA and non HLA factors that affect donor choices, and the outstanding comparative outcome studies of different donor usage in hematologic malignancies.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762776","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}
Deepa Gautam, Emily M Clarke, Harvey G Roweth, Margaret R Smith, Elisabeth M Battinelli
{"title":"Platelets and circulating (and tumor) cells: partners in promoting metastatic cancer.","authors":"Deepa Gautam, Emily M Clarke, Harvey G Roweth, Margaret R Smith, Elisabeth M Battinelli","doi":"10.1097/MOH.0000000000000852","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000852","url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite being discovered decades ago, metastasis remains a formidable challenge in cancer treatment. During the intermediate phase of metastasis, tumor cells detach from primary tumor or metastatic sites and travel through the bloodstream and lymphatic system to distant tissues. These tumor cells in the circulation are known as circulating tumor cells (CTCs), and a higher number of CTCs has been linked to poor prognoses in various cancers. The blood is an inhospitable environment for any foreign cells, including CTCs, as they face numerous challenges, such as the shear stress within blood vessels and their interactions with blood and immune cells. However, the exact mechanisms by which CTCs survive the hostile conditions of the bloodstream remain enigmatic. Platelets have been studied for their interactions with tumor cells, promoting their survival, growth, and metastasis. This review explores the latest clinical methods for enumerating CTCs, recent findings on platelet-CTC crosstalk, and current research on antiplatelet therapy as a potential strategy to inhibit metastasis, offering new therapeutic insights.</p><p><strong>Recent findings: </strong>Laboratory and clinical data have provided insights into the role of platelets in promoting CTC survival, while clinical advancements in CTC enumeration offer improved prognostic tools.</p><p><strong>Summary: </strong>CTCs play a critical role in metastasis, and their interactions with platelets aid their survival in the hostile environment of the bloodstream. Understanding this crosstalk offers insights into potential therapeutic strategies, including antiplatelet therapy, to inhibit metastasis and improve cancer treatment outcomes.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589968","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}
Justin S Trory, Jordan Vautrinot, Carl J May, Ingeborg Hers
{"title":"PROTACs in platelets: emerging antithrombotic strategies and future perspectives.","authors":"Justin S Trory, Jordan Vautrinot, Carl J May, Ingeborg Hers","doi":"10.1097/MOH.0000000000000846","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000846","url":null,"abstract":"<p><strong>Purpose of review: </strong>Proteolysis-targeted chimeras (PROTACs) are heterobifunctional compounds that selectively target proteins for degradation and are an emerging therapeutic modality to treat diseases such as cancer and neurodegenerative disorders. This review will widen the area of application by highlighting the ability of PROTACs to remove proteins from the anucleate platelets and evaluate their antithrombotic potential.</p><p><strong>Recent findings: </strong>Proteomic and biochemical studies demonstrated that human platelets possess the Ubiquitin Proteasomal System as well as the E3 ligase cereblon (CRBN) and therefore may be susceptible to PROTAC-mediated protein degradation. Recent findings confirmed that CRBN ligand-based PROTACs targeting generic tyrosine kinases, Btk and/or Fak lead to efficacious and selective protein degradation in human platelets. Downregulation of Btk, a key player involved in signalling to thrombosis, but not haemostasis, resulted in impaired in-vitro thrombus formation.</p><p><strong>Summary: </strong>Platelets are susceptible to targeted protein degradation by CRBN ligand-based PROTACs and have limited ability to resynthesise proteins, ensuring long-term downregulation of target proteins. Therefore, PROTACs serve as an additional research tool to study platelet function and offer new therapeutic potential to prevent thrombosis. Future studies should focus on enhancing cell specificity to avoid on-target side effects on other blood cells.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513344","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}
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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}