Abstract:
PURPOSE OF REVIEW:The polycomb group gene BMI1 fulfills essential roles in both normal and leukemic stem cells. The underlying molecular mechanisms are beginning to become unraveled and an overview of the current knowledge on BMI1 signaling in normal and leukemic stem cells will be presented here. RECENT FINDINGS:In addition to a role in bypassing senescence and the orchestration of the symmetry of hematopoietic stem cell divisions, it has recently become clear that BMI1 also functions in the protection against oxidative stress. In the absence of BMI1, reactive oxygen species accumulate, associating with activation of DNA damage response pathways and increased apoptosis. BMI1-mediated control over reactive oxygen species levels might occur independently of the INK4a/ARF pathway, but rather involves impaired mitochondrial functions. In human hematopoietic malignancies, BMI1 is frequently overexpressed, which associates with poor prognosis. Down modulation of BMI1 impairs self-renewal and long-term expansion of leukemic stem cells. SUMMARY:Understanding molecular mechanisms by which BMI1 affects stem cell fate will increase our insights into the biology of hematopoietic stem cells and will also aid in understanding the process of leukemic transformation and ultimately in the identification of drugable targets that might facilitate the eradication of leukemic stem cells.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Schuringa JJ,Vellenga Edoi
10.1097/MOH.0b013e328338c439subject
Has Abstractpub_date
2010-07-01 00:00:00pages
294-9issue
4eissn
1065-6251issn
1531-7048journal_volume
17pub_type
杂志文章,评审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:This review is designed to help readers understand seasonal blood shortages and provide solutions through the use of technology that can increase the number of red blood cell units collected and the use of recruitment and marketing initiatives that appeal to the increasingly diverse donor base. RECEN...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:10.1097/01.moh.0000180436.98990.ce
更新日期:2005-11-01 00:00:00
abstract::Several methods to model human Ph+ leukemia in laboratory mice are available, including propagation of BCR/ABL-expressing cells in mice, xenotransplantation of primary Ph+ leukemia cells into immunodeficient mice, BCR/ABL transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. Recent stud...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200107000-00008
更新日期:2001-07-01 00:00:00
abstract::Gene transfer has allowed a number of biologic issues in the therapy of hematologic malignancy to be addressed. In autologous bone marrow transplantation, gene marking studies have shown that infused marrow contributes to relapse in acute myeloid leukemia, neuroblastoma, and chronic myeloid leukemia. In addition, doub...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502060-00004
更新日期:1995-11-01 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:The discovery of JAK2V617F and other JAK-STAT-activating mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPN) has led to the development of small-molecule ATP-mimetics that inhibit wild-type and mutant JAK. Here, we review the current experience with JAK inhibitors used for the treatment ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283439964
更新日期:2011-03-01 00:00:00
abstract::The advent of better diagnostic tools, molecular techniques, and cytokine therapies have come together at the end of the 20th century to provide an improved outlook for patients with autoimmune neutropenia. Severe chronic neutropenia is no longer idiopathic in most cases, and growth factor therapy can be safely offere...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200105000-00007
更新日期:2001-05-01 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:PURPOSE OF REVIEW:The peptide hormone hepcidin regulates iron metabolism in response to erythropoietic demand, iron stores and inflammation. Major advances have been made in understanding the regulation of hepcidin production, and consequently the availability of iron for erythropoiesis. RECENT FINDINGS:It is becoming...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282f73335
更新日期:2008-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Immune responses to commensal bacteria and resulting chronic inflammation are hallmarks of inflammatory bowel disease. Considerable evidence has accumulated to suggest that innate immune defense mechanisms interact with pro-inflammatory pathways and exacerbate or perhaps even initiate development of i...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200701000-00010
更新日期:2007-01-01 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: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::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::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::Human immunodeficiency virus infection causes multilineage hematopoietic defects. Defects in the production and function of CD4+ helper cells have been the focus of the majority of HIV research, but anemia, neutropenia, and thrombocytopenia are significant clinical problems as well. Bone marrow suppression is the dose...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502030-00012
更新日期:1995-05-01 00:00:00
abstract::Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion therapy has not been determined for most clinical settings. Recent research has focused on controlled studies of red cell transfusion in specific clinical settings. Better determinations of oxygen delivery and consumption are ...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:10.1097/00062752-200111000-00012
更新日期:2001-11-01 00:00:00
abstract::Bone marrow transplantation protocols for inherited metabolic storage diseases are unique for each disorder treated. Differences depend also upon how old the patient was when onset occurred and rate of progression of disease. Treatment is directed to prevent or ameliorate the inexorable neurological deterioration that...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199911000-00004
更新日期:1999-11-01 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:PURPOSE OF REVIEW:Chronic inflammation and disordered lipid metabolism represent hallmarks of atherosclerosis. Considerable evidence has accumulated to suggest that innate immune defense mechanisms might interact with proinflammatory pathways and exacerbate or perhaps even initiate development of arterial plaques. Unti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000219662.88409.7c
更新日期:2006-05-01 00:00:00
abstract:PURPOSE OF REVIEW:The purpose of this review is to describe the physiopathological and therapeutic aspects of neutrophilic dermatosis, taking into account their most frequent associated conditions. RECENT FINDINGS:In autoinflammatory syndromes featuring neutrophilic dermatosis, the role of interleukin-1 and tumor necr...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000100
更新日期:2015-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Despite parenteral artesunate therapy, the fatality rate of cerebral malaria remains high. Adjunctive therapy targeting the underlying pathophysiology of cerebral malaria may further improve the clinical outcome. Endothelial activation and dysfunction is a central process in the pathogenesis of cerebr...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328345a4cf
更新日期:2011-05-01 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: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:PURPOSE OF REVIEW:Fibroblast growth factor (FGF) signaling activates many bone marrow cell types, including various stem cells, osteoblasts, and osteoclasts. However, the role of FGF signaling in regulation of normal and leukemic stem cells is poorly understood. This review highlights the physiological roles of FGF sig...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283606162
更新日期:2013-05-01 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: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:PURPOSE OF REVIEW:In this review, we focus on three specific concepts related to platelet transfusion in the neonatal and pediatric population: choice of transfusion threshold; use of ABO-mismatched platelets; transfusion of pathogen-reduced or inactivated platelets. RECENT FINDINGS:Recent trials support the use of lo...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000542
更新日期:2019-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Vasculogenesis and hematopoiesis are essential for development. Recently, the ETS domain transcription factor Etv2 has been identified as an essential regulator of vasculogenesis and hematopoiesis. Here, we review the recent studies that have established the critical role of Etv2 in the specification ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283523e07
更新日期:2012-05-01 00:00:00
abstract:PURPOSE OF REVIEW:To highlight mechanisms that regulate the balance between latent and active von Willebrand factor (VWF), and describe pathological conditions leading to increased levels of active VWF. RECENT FINDINGS:Levels of circulating active VWF are increased in von Willebrand disease type 2B, HELLP syndrome, ma...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280dce531
更新日期:2007-05-01 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