Abstract:
:The transcription factor signal transducer and activator of transcription 5 (STAT5) fulfills essential roles in self-renewal in mouse and human hematopoietic stem cells (HSCs), and its persistent activation contributes to leukemic transformation, although little molecular insight into the underlying mechanisms has been obtained. In the present study, we show that STAT5 can impose long-term expansion exclusively on human HSCs, not on progenitors. This was associated with an enhanced cobblestone formation under bone marrow stromal cells of STAT5-transduced HSCs. Hypoxia-induced factor 2α (HIF2α) was identified as a STAT5 target gene in HSCs, and chromatin immunoprecipitation studies revealed STAT5 binding to a site 344 base pairs upstream of the start codon of HIF2α. Lentiviral RNA interference (RNAi)-mediated down-modulation of HIF2α impaired STAT5-induced long-term expansion and HSC frequencies, whereas differentiation was not affected. Glucose uptake was elevated in STAT5-activated HSCs, and several genes associated with glucose metabolism were up-regulated by STAT5 in an HIF2α-dependent manner. Our studies indicate that pathways normally activated under hypoxia might be used by STAT5 under higher oxygen conditions to maintain and/or impose HSC self-renewal properties.
journal_name
Bloodjournal_title
Bloodauthors
Fatrai S,Wierenga AT,Daenen SM,Vellenga E,Schuringa JJdoi
10.1182/blood-2010-08-303669subject
Has Abstractpub_date
2011-03-24 00:00:00pages
3320-30issue
12eissn
0006-4971issn
1528-0020pii
blood-2010-08-303669journal_volume
117pub_type
杂志文章相关文献
BLOOD文献大全abstract::Continuous treatment of malignancies with tyrosine kinase inhibitors (TKIs) may select for resistant clones (ie, imatinib mesylate). To study resistance to TKIs targeting FLT3, a receptor tyrosine kinase that is frequently mutated in acute myelogenous leukemia (AML), we developed resistant human cell lines through pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-023804
更新日期:2007-02-15 00:00:00
abstract::What are the rules that govern a naive T cell's prospects for survival or division after export from the thymus into the periphery? To help address these questions, we combine data from existing studies with robust mathematical models to estimate the absolute contributions of thymopoiesis, peripheral division, and los...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-10-184184
更新日期:2009-05-28 00:00:00
abstract::Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis vir...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2010-06-275818
更新日期:2011-02-10 00:00:00
abstract::The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was ex...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::In this issue of Blood, Vérollet et al show that expression of the HIV-1–derived protein Nef alters the migratory mode adopted by macrophages, enhancing macrophage tissue infiltration and explaining the observed accumulation of tissue-resident macrophages in some HIV-infected patients. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-01-618983
更新日期:2015-03-05 00:00:00
abstract::Erythropoietin (EPO) is required for the survival and expansion of red blood cell progenitor cells and supports continued differentiation of these committed progenitors to mature red blood cells. After binding to its cognate receptor, EPO promotes receptor homodimerization, activation of receptor-associated JAK2, subs...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-10-15 00:00:00
abstract::The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Hypodiploidy <40 chromosomes is an uncommon genetic feature of acute lymphoblastic leukemia (ALL) in both children and adults. It has long been clear by cytogenetic analyses, and recently confirmed by mutational profiling, that these cases may be further subdivided into 2 subtypes: near-haploid ALL with 24 to 30 chrom...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-10-743765
更新日期:2017-01-26 00:00:00
abstract::Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus rema...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-06-291690
更新日期:2011-01-27 00:00:00
abstract::Platelet-von Willebrand factor (VWF) interactions must be tightly regulated in order to promote effective hemostasis and prevent occlusive thrombus formation. However, it is unclear what role the inherent properties of the bond formed between the platelet receptor glycoprotein Ibα and the A1 domain of VWF play in thes...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-04-569392
更新日期:2014-12-11 00:00:00
abstract::Chromosomal abnormalities in acute leukemia have led to the discovery of many genes involved in normal hematopoiesis and in malignant transformation. We have identified the fusion partners in an inv(8)(p11q13) from a patient with acute mixed lineage leukemia. We show by fluorescence in situ hybridization (FISH) analys...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-09-15 00:00:00
abstract::To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cel...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-05-15 00:00:00
abstract::The FOXP1 forkhead transcription factor is targeted by recurrent chromosome translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high-level FOXP1 protein expression has been linked to a poor prognosis. Western blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly identi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-115113
更新日期:2008-03-01 00:00:00
abstract::Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We ra...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-316885
更新日期:2011-05-05 00:00:00
abstract::Understanding leukemia heterogeneity is critical for the development of curative treatments as the failure to eliminate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse. Here we have combined high-throughput immunophenotypic screens with large-scale single-cell gene expression analysis to de...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-07-728873
更新日期:2017-04-27 00:00:00
abstract::Platelet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 microg/mL but not afte...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2363
更新日期:2003-06-15 00:00:00
abstract::Whole saliva samples collected from available people at risk in Boston for infection with human T-lymphotropic virus type III (HTLV-III/LAV), from late 1984 through early 1985, were analyzed for the presence of antibodies to viral proteins. Fourteen of 20 (70%) acquired immunodeficiency syndrome (AIDS) patients and 14...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Numerous studies have reported significant associations between ABO blood group and risk of cardiovascular disease. These studies have consistently demonstrated that thrombotic risk is significantly reduced in individuals in blood group O. Nevertheless, the biological mechanisms through which ABO influences hemostasis...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005843
更新日期:2020-12-17 00:00:00
abstract::Andexanet alfa, a reversing agent for anticoagulants that inhibit factor Xa, has recently been licensed in the United States. We discuss the impact of this licensure on current practice and review in detail the problems of a neglected and growing clinical area: reversing the anticoagulation effect of factor Xa inhibit...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2018-06-850396
更新日期:2018-12-06 00:00:00
abstract::Complement plays a key role in host defense, but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins, including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-07-728253
更新日期:2017-03-02 00:00:00
abstract::In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. A...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2006-09-045369
更新日期:2007-09-01 00:00:00
abstract::Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutation...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-282541
更新日期:2010-10-14 00:00:00
abstract::We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with > 1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-339879
更新日期:2011-12-08 00:00:00
abstract::Lipoxygenases (LXs) catalyze formation of leukotrienes and hydroxy-eicosatetraenoic acids (HETEs), proinflammatory, and spasmogenic autacoids that are critical for host defense systems. We studied the expression and regulation of LX genes (12-LX, 5-LX, and 15-LX) and the 5-lipoxygenase activating protein (FLAP) in hum...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Plasmodium falciparum-infected erythrocytes (parasitized red blood cells [PRBCs]) can adhere to uninfected erythrocytes (RBCs) to form rosettes, and adhere to the endothelial cell (EC) surface antigen CD36. These adherence phenomena have previously been considered quite different. We show that anti-CD36 monoclonal ant...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-10-15 00:00:00
abstract::In this issue of Blood, Jodele and colleagues report that defective complement regulation contributes to the development of thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) with important implications for diagnosis and management of this severe clinical complication. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2013-07-512707
更新日期:2013-09-19 00:00:00
abstract::Cytokine gene-modified tumor cells have increased immunogenicity and retain the antigenic repertoire of a particular neoplasia. However, practical concerns have led to an increased interest in allogeneic gene-transduced bystander cells as a broader source of cytokines for autologous tumor cell-based vaccines. Here, we...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-03-0991
更新日期:2003-01-15 00:00:00
abstract::Mycophenolate mofetil (MMF) was evaluated either alone or combined with cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts. Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four groups wer...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::Protein S, an inhibitor of coagulation, interacts reversibly with C4b binding protein (C4bBP). The physiologic role of this complex formation remains unknown. In this study we examined the possibility that protein S would facilitate C4bBP binding to the surface of neutrophils where, in turn, this complex could help pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-01-15 00:00:00
abstract::Sequential immunologic, cytochemical, and cytokinetic studies were done on single lymphoid cells in the peripheral blood of 6 children with infectious mononucleosis (IM) and 1 child with toxoplasmosis 1-2 wk after onset of symptomatology. The absolute number of AET-SRBC rosetting (E+) cells was increased in all patien...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00