Abstract:
PURPOSE OF REVIEW:Mutations in the Endoglin (Eng) gene, an auxiliary receptor in the transforming growth factor beta (TGFβ)-superfamily signaling pathway, are responsible for the human vascular disorder hereditary hemorrhagic telangiectasia (HHT) type 1, characterized in part by blood vessel enlargement. A growing body of work has uncovered an autonomous role for Eng in endothelial cells. We will highlight the influence of Eng on distinct cellular behaviors, such as migration and shape control, which are ultimately important for the assignment of proper blood vessel diameters. RECENT FINDINGS:How endothelial cells establish hierarchically ordered blood vessel trees is one of the outstanding questions in vascular biology. Mutations in components of the TGFβ-superfamily of signaling molecules disrupt this patterning and cause arteriovenous malformations (AVMs). Eng is a TGFβ coreceptor enhancing signaling through the type I receptor Alk1. Recent studies identified bone morphogenetic proteins (BMPs) 9 and 10 as the primary ligands for Alk1/Eng. Importantly, Eng potentiated Alk1 pathway activation downstream of hemodynamic forces. New results furthermore revealed how Eng affects endothelial cell migration and cell shape control in response to these forces, thereby providing new avenues for our understanding of AVM cause. SUMMARY:We will discuss the interplay of Eng and hemodynamic forces, such as shear stress, in relation to Alk1 receptor activation. We will furthermore detail how this signaling pathway influences endothelial cell behaviors important for the establishment of hierarchically ordered blood vessel trees. Finally, we will provide an outlook how these insights might help in developing new therapies for the treatment of HHT.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Sugden WW,Siekmann AFdoi
10.1097/MOH.0000000000000419subject
Has Abstractpub_date
2018-05-01 00:00:00pages
237-244issue
3eissn
1065-6251issn
1531-7048journal_volume
25pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:Chronic idiopathic and severe congenital neutropenias are rare disorders for which recent discoveries have highlighted mechanisms and consequences. RECENT FINDINGS:An inflammatory bone marrow milieu has been shown to be a major contributor to the pathophysiology of chronic idiopathic neutropenia. Act...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282f172d3
更新日期:2008-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic stem cells are functionally heterogeneous even when isolated as phenotypically homogenous populations. How this heterogeneity is generated is incompletely understood. Several models have been formulated to explain the generation of diversity. All of these assume the existence of a single...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000231421.00407.65
更新日期:2006-07-01 00:00:00
abstract::Neutropenia is often attributed to immunologically mediated injury to mature neutrophils or their precursors. Clinically it is useful to classify immune mediated neutropenias as isoimmune, autoimmune (including some drug-associated neutropenias), and idiopathic (cases possibly with an immune mechanism). Isoimmune neut...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199801000-00006
更新日期:1998-01-01 00:00:00
abstract::The reconstitution of T-cell populations is a critical component of immune recovery after allogeneic stem cell transplantation. Recent studies have used new techniques to focus on the interplay of thymopoiesis and peripheral expansion that defines T-cell repopulation. Peripheral expansion, driven by host cytokines and...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200211000-00004
更新日期:2002-11-01 00:00:00
abstract::Fibrinogen abnormalities can be classified as congenital or acquired. Each class manifests quantitative or qualitative alterations; the latter are known as dysfibrinogenemias. In dysfibrinogenemias, structural defects cause alterations in the conversion of fibrinogen to fibrin. Approximately 300 abnormal fibrinogens h...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704050-00010
更新日期:1997-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Angioimmunoblastic T cell lymphoma is a complex lymphoproliferative disorder. While recent evidence suggests that the Epstein-Barr virus and B cell disregulation are implicated in the disease's pathogenesis, their mechanistic roles remain largely unknown. The prognosis with traditional chemotherapy ha...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328186ffbf
更新日期:2007-07-01 00:00:00
abstract::Many aspects of leukocyte function are regulated by both heterotrimeric and Ras-related GTP-binding proteins, but there is little definite information about their roles in the specialized processes utilized by leukocytes for cell killing. Recent progress in understanding the regulation of the phagocyte NADPH oxidase b...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Human parvovirus B19 shows remarkable tropism for human erythroid progenitor cells. The pathogenesis of disease resulting from infection is a dynamic between the viral suppression of erythropoiesis and the host's ability to mount an effective immune response. Understanding this process has led to strategies for treati...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199603020-00002
更新日期:1996-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Graft-versus-host disease is one of the commonest complications of allogeneic bone marrow or peripheral blood stem cell transplantation. This review will cover advances in the pathophysiology of graft-versus-host disease and new agents under investigation for the treatment of this disorder. Patients d...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000148763.12733.bb
更新日期:2005-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), despite improvements in our understanding of its pathophysiology as well as the generation of new monoclonal antibodies, immunomodulatory chemotherapy, cellular ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283319a6f
更新日期:2009-11-01 00:00:00
abstract:PURPOSE OF REVIEW:This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000401
更新日期:2018-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Microtransplantation (MST) has been successfully used to manage patients with hematological malignancies, especially older patients with acute myeloid leukemia (AML). Recent clinical applications and mechanistic studies of MST are reviewed. RECENT FINDINGS:MST improves complete remission rates which ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000470
更新日期:2018-11-01 00:00:00
abstract::Matching for human leukocyte antigen (HLA) loci is the most crucial factor in the selection of bone marrow donors. The techniques utilized to assign HLA type have evolved significantly since the application of polymerase chain reaction-based methodologies. A significant challenge for DNA typing methodologies is to be ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199811000-00012
更新日期:1998-11-01 00:00:00
abstract::The Epstein-Barr virus is a ubiquitous human herpesvirus that is associated with an increasing number of human malignancies. Among these are Epstein-Barr virus-associated lymphoproliferative diseases in immunocompromised patients, a spectrum of mainly B-cell diseases that range from polyclonal lymphoproliferative dise...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199901000-00005
更新日期:1999-01-01 00:00:00
abstract::Chronic myelogenous leukemia is a clonal hematopoietic malignancy characterized by a balanced translocation between chromosomes 9 and 22 that results in the generation of an abnormal bcr/abl fusion protein with increased tyrosine kinase activity. This abnormal fusion protein has transforming activity for hematopoietic...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502040-00009
更新日期:1995-07-01 00:00:00
abstract:PURPOSE OF REVIEW:In response to agonists produced at vascular lesions, platelets release a host of components from their three granules: dense core, alpha, and lysosome. This releasate activates other platelets, promotes wound repair, and initiates inflammatory responses. Although widely accepted, the specific mechani...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328309ec74
更新日期:2008-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic cell transplantation offers potentially curative therapy for patients with myelodysplastic syndrome. The median patient age at diagnosis, however, is about 70 years, which has limited the application of conventional hematopoietic cell transplantation. In addition, the optimum timing of t...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000208466.63861.9f
更新日期:2006-03-01 00:00:00
abstract::Recent advances in our understanding of hypereosinophilia have related particularly to the definition of criteria for distinguishing between eosinophilic leukemia and the 'idiopathic' hypereosinophilic syndromes. In this article, leukemogenic mechanisms have been identified in a number of subtypes of eosinophilic leuk...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200001000-00005
更新日期:2000-01-01 00:00:00
abstract::The molecular analysis of genetic alterations in acute lymphoblastic leukemia has led to the development of molecular diagnostic techniques that have improved the biologic characterization of newly diagnosed patients. Modern treatment protocols rely on this information to tailor the intensity of therapy to the risk of...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704040-00003
更新日期:1997-07-01 00:00:00
abstract:PURPOSE OF REVIEW:To discuss how mechanical cues and Rho signaling contribute to control of vascular development and hematopoiesis. RECENT FINDINGS:Rho guanine trinucleotide phosphatases are ubiquitious regulators of cytoskeletal structure and tension generation. Recent work shows that Rho-dependent mechanical interac...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282fa7445
更新日期:2008-05-01 00:00:00
abstract:PURPOSE OF REVIEW:To examine the current literature regarding retrievable inferior vena cava filters and to discuss the appropriate indications for their clinical use. RECENT FINDINGS:Permanent filters have been shown to be effective, but have a number of long-term complications such as filter thrombosis or migration....
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000239707.63168.ee
更新日期:2006-09-01 00:00:00
abstract::Much progress has been made in delineating the pathogenesis of multiple myeloma and chronic lymphocytic leukemia. The cell of origin in both diseases has been better defined, which has led to important clinical treatments. For myeloma, reduction of tumor burden in autografts has been accomplished and been associated w...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199603040-00007
更新日期:1996-07-01 00:00:00
abstract::Each year, approximately one in 1000 individuals suffers from venous thromboembolism. The pathogenesis of the disease is multifactorial and a thrombotic event is the result of a combination of genetic and circumstantial risk factors. Until recently, genetic defects could only be identified in a minority of thrombosis ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502050-00006
更新日期:1995-09-01 00:00:00
abstract::Following on the heels of multiple failed clinical trials of adjunctive therapeutic agents in sepsis, the positive outcome of a recent phase III study using activated protein C (APC) has led to a renewed optimism in targeted biotherapies for this syndrome. A growing body of data (both preclinical and clinical) suggest...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200209000-00005
更新日期:2002-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Defensins are a major family of antimicrobial peptides expressed predominantly in neutrophils and epithelial cells, and play important roles in innate immune defense against infectious pathogens. Their biological functions in and beyond innate immunity, structure and activity relationships, mechanisms...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000005
更新日期:2014-01-01 00:00:00
abstract:PURPOSE OF REVIEW:The advent of tyrosine kinase inhibitors (TKI) has remarkably changed the treatment of chronic myeloid leukemia (CML). Patients treated in chronic phase can enjoy an expected survival similar to the general population. In the last few years we have found that some patients with an excellent therapeuti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000224
更新日期:2016-03-01 00:00:00
abstract::The advent of safe and practical means to correct, enhance or protect blood cells at the genetic level offers tantalizing therapeutic perspectives. At present, gene delivery using a replication-defective retrovirus is the most efficient method to stably transduce hematopoietic cells. The successful adaptation of retro...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200011000-00008
更新日期:2000-11-01 00:00:00
abstract:PURPOSE OF REVIEW:New discoveries focused on mitochondrial metabolism and gene silencing and their regulation by the sirtuin family of protein deacetylases is stimulating new ideas on how to improve geriatric medicine. Information about sertuins in stem cell biology is scarce. We consider recent information on sirtuin ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283043819
更新日期:2008-07-01 00:00:00
abstract:PURPOSE OF REVIEW:Therapy-related myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) comprise an increasingly common, poor-risk disease cohort without standard treatment options. This review describes available treatments and recent advances that may influence the clinical management of t-MDS/AML. RE...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32835d82e6
更新日期:2013-03-01 00:00:00
abstract::Considerable data now support the hypothesis that platelets actively regulate the propagation of coagulation by (1) expressing specific, high-affinity receptors for coagulation proteases, zymogens, and cofactors; (2) protecting the bound coagulation enzymes from inactivation/inhibition; (3) restricting coagulant activ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200109000-00001
更新日期:2001-09-01 00:00:00