Abstract:
PURPOSE OF REVIEW:A major goal in repopulating hematopoietic stem cell (HSC) gene therapies is achieving high-efficacy gene transfer, while maintaining robust HSC engraftment and differentiation in vivo. Recent studies have documented that rapamycin treatment of HSC during lentiviral vector transduction enhances gene transfer to human and mouse HSCs and maintains engraftment capacity. In this review, we place into context the role of mammalian target of rapamycin (mTOR) pathways in HSC quiescence and function, endocytic regulation, and lentiviral gene delivery. RECENT FINDINGS:Lentiviral vector transduction of human and mouse HSCs is considerably enhanced by rapamycin treatment. Furthermore, rapamycin preserves long-term engraftment of human and mouse HSCs. Investigations of cellular mechanisms that contribute to increased transduction in HSCs uncover a role for mTOR inhibition-dependent activation of endocytosis. SUMMARY:Rapamycin enhances lentiviral vector transduction of HSCs through regulation of endocytic activity via mTOR inhibition. An important attribute of rapamycin treatment during transduction is the preservation of HSC function, allowing reconstitution of long-term hematopoiesis in vivo in murine models.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Wang CX,Torbett BEdoi
10.1097/MOH.0000000000000150subject
Has Abstractpub_date
2015-07-01 00:00:00pages
302-8issue
4eissn
1065-6251issn
1531-7048pii
00062752-201507000-00006journal_volume
22pub_type
杂志文章,评审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:The identification of regulatory T cells (Tregs) as regulators of immunological self-tolerance has stimulated tremendous interest in the field. Over the past 12 months, new studies have added greatly to our understanding of the role of Tregs in autoimmune disease, details of which are presented here. ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832a9a01
更新日期:2009-07-01 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:PURPOSE OF REVIEW:The leukocyte adhesion deficiency (LAD) syndromes are rare genetically determined conditions with challenging clinical features. These immunodeficiencies also provide insights that are broadly relevant to the biology of leukocytes, platelets, intercellular interactions, and intracellular signaling. Re...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32835a0091
更新日期:2013-01-01 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:PURPOSE OF REVIEW:B-cell tumors originating from the transformation of germinal center B cells frequently harbor genetic mutations, leading to constitutive activation of the nuclear factor-κB (NF-κB) signaling pathway. The present review highlights recent insights into the roles of separate NF-κB transcription factors ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000160
更新日期:2015-07-01 00:00:00
abstract::Genetic defects of the blood platelet membrane glycoproteins, GPIIb-IIIa (alpha IIb/beta 3; CD41/CD61) and GPIb-V-IX (CD42) are the origin of several rare bleeding disorders, the best known of which are Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and platelet-type von Willebrand's disease. In Glanzmann's thr...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1994-09-01 00:00:00
abstract::Although the mature enucleated erythrocyte is no longer active in nuclear processes such as pre-mRNA splicing, the function of many of its major structural proteins is dependent on alternative splicing choices made during the earlier stages of erythropoiesis. These splicing decisions fundamentally regulate many aspect...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200103000-00003
更新日期:2001-03-01 00:00:00
abstract::Platelet aggregation, a process mediated by GP IIb-IIIa, is responsible for the occlusive events in thrombosis: indeed, GP IIb-IIIa antagonists are effective in blocking arterial thrombosis. Recent studies have suggested that activated platelets and platelet thrombi can contribute significantly to the initiation and p...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200309000-00006
更新日期:2003-09-01 00:00:00
abstract::This overview concentrates on familial and congenital polycythemias in the context of other polycythemic disorders, with emphasis on those with established molecular lesions. Recent advances in the regulation of erythropoiesis, as they may relate to polycythemic states, are discussed as a background for those well-def...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199903000-00008
更新日期:1999-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with seve...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000424
更新日期:2018-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Platelet microparticles were identified more than 40 years ago and are the most abundant circulating microparticle subtype. Yet fundamental questions about their formation and role in human disease are just beginning to be understood at the cellular and molecular level. This review will address mechan...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32833e77ee
更新日期:2010-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000350
更新日期:2017-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Management of these patients must take into account patient and leukemia-related factors in order to organize a comprehensive approach to treatment. Many new therapies are under study. RECENT FINDINGS:Ne...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32801684ef
更新日期:2007-03-01 00:00:00
abstract::When a new product with huge clinical potential explodes on the scene, the hope is that the benefits far outweigh the risks in long-term administration. After 10 years of clinical use, granulocyte colony-stimulating factor (G-CSF) has lived up to that promise so far. In the context of severe chronic neutropenia, more ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704030-00011
更新日期:1997-05-01 00:00:00
abstract:PURPOSE OF REVIEW:This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction. RECENT FINDINGS:Autoantibodies are produced by a limited number...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282ba5552
更新日期:2007-09-01 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
abstract:PURPOSE OF REVIEW:There are three kindlin family members in vertebrates, which have high-sequence homology and a common organization signature with a C-terminal 4.1, ezrin, radixin, moesin (FERM) domain bisected by a pleckstrin-homology domain. Although the cell and tissue distributions of the three kindlins differ, th...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832ea389
更新日期:2009-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Type 1 von Willebrand disease (VWD) is the most common form of VWD, but has remained [corrected] the least well understood. Recent work is changing this situation. This review summarizes recent analysis of the genetic basis of the disease. RECENT FINDINGS:Linkage analysis demonstrates that dominantly...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32826f4b41
更新日期:2007-09-01 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:PURPOSE OF REVIEW:In the postnatal life, hematopoietic stem cell (HSC) niches are specialized microenvironments in the bone marrow that are essential for the maintenance and function of HSCs. The purpose of this review is to discuss the concept of HSC niche in light of recent studies that broaden its complexity and bet...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32833a25d8
更新日期:2010-07-01 00:00:00
abstract::Myeloablative therapy followed by autologous bone marrow or peripheral blood stem cell rescue is an alternative therapeutic option for patients who are not candidates for allogeneic transplantation due to the lack of an appropriate HLA-matched donor or to advanced age. It allows therapy to be administered that is of c...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704060-00011
更新日期:1997-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Mortality and morbidity associated with leukemia are largely due to frequently occurring cytopenias or the dysfunction of normal blood cells in patients. Our knowledge of how normal blood cells degenerate in response to leukemic cell infiltration has been quite limited. This review summarizes recent f...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000253
更新日期:2016-07-01 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::Cytomegalovirus (CMV) infection remains a major cause of morbidity and mortality in recipients of an allogeneic stem cell transplant (SCT). Due to the broad application of antiviral prophylaxis and preemptive therapy, a decrease in early-onset and a subsequent increase in late-onset CMV disease has been observed. New ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199811000-00022
更新日期:1998-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Glycogen storage disease Ib (GSD Ib) is characterized by hepatomegaly, hypoglycemia, neutropenia, enterocolitis and recurrent bacterial infections. It is attributable to mutations in G6PT1, the gene for the glucose-6-phosphate transporter responsible for transport of glucose into the endoplasmic retic...
journal_title:Current opinion in hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/MOH.0000000000000474
更新日期:2019-01-01 00:00:00
abstract::Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a transl...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200005000-00003
更新日期:2000-05-01 00:00:00
abstract::A variety of agents are available to improve hemostasis and reduce blood loss in multiple clinical settings. These agents are most commonly used to reduce bleeding when an underlying hemostatic defect is present. Some new agents offer the potential to decrease blood loss even in the absence of an obvious underlying he...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200211000-00014
更新日期:2002-11-01 00:00:00
abstract::Within the past year substantial progress has been made in understanding the molecular changes underlying the development of acute leukemia. Development of molecular probes allowed substantial improvements in the detection of minimal residual disease. Pilot studies underlined the correlation between the expression of ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1994-07-01 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