Abstract:
:Neutrophilic differentiation is dependent on CCAAT enhancer-binding protein α (C/EBPα), a transcription factor expressed in multiple organs including the bone marrow. Using functional genomic technologies in combination with clustered regularly-interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing and in vivo mouse modeling, we show that CEBPA is located in a 170-kb topological-associated domain that contains 14 potential enhancers. Of these, 1 enhancer located +42 kb from CEBPA is active and engages with the CEBPA promoter in myeloid cells only. Germ line deletion of the homologous enhancer in mice in vivo reduces Cebpa levels exclusively in hematopoietic stem cells (HSCs) and myeloid-primed progenitor cells leading to severe defects in the granulocytic lineage, without affecting any other Cebpa-expressing organ studied. The enhancer-deleted progenitor cells lose their myeloid transcription program and are blocked in differentiation. Deletion of the enhancer also causes loss of HSC maintenance. We conclude that a single +42-kb enhancer is essential for CEBPA expression in myeloid cells only.
journal_name
Bloodjournal_title
Bloodauthors
Avellino R,Havermans M,Erpelinck C,Sanders MA,Hoogenboezem R,van de Werken HJ,Rombouts E,van Lom K,van Strien PM,Gebhard C,Rehli M,Pimanda J,Beck D,Erkeland S,Kuiken T,de Looper H,Gröschel S,Touw I,Bindels E,Delweldoi
10.1182/blood-2016-01-695759subject
Has Abstractpub_date
2016-06-16 00:00:00pages
2991-3003issue
24eissn
0006-4971issn
1528-0020pii
blood-2016-01-695759journal_volume
127pub_type
杂志文章相关文献
BLOOD文献大全abstract::Essential thrombocythemia (ET) and polycythemia vera (PV) are characterized by persistent platelet activation. The mechanisms involved in their clearance are poorly characterized. In the present study, we report that leukocytes were actively involved in platelet disposal in 51 patients with ET and 30 with PV, but not ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-337337
更新日期:2011-09-22 00:00:00
abstract::Functional studies on native human dendritic cells (DCs) are hampered by technical difficulties in preparing fresh DCs. Recently, with the help of the monoclonal antibody M-DC8, we succeeded in isolating a major subpopulation of human blood DCs by a one-step immunomagnetic separation procedure. These cells strongly ex...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::Sixteen patients with adult T-cell leukemia/lymphoma (ATL) who were all over 50 years of age underwent allogeneic stem cell transplantation with reduced-conditioning intensity (RIST) from HLA-matched sibling donors after a conditioning regimen consisting of fludarabine (180 mg/m2), busulfan (8 mg/kg), and rabbit antit...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-11-4193
更新日期:2005-05-15 00:00:00
abstract::We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::The proapoptotic function of p53 is thought to underlie most anticancer modalities and is also activated in response to oncogenic insults, such as overexpression of the Myc oncoprotein. Here we generated tractable B lymphomas using retroviral transduction of the MYC oncogene into hematopoietic cells with 2 knock-in al...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-050294
更新日期:2007-06-01 00:00:00
abstract::Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluor...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-07-15 00:00:00
abstract::Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation s...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-03-494039
更新日期:2013-07-04 00:00:00
abstract::A simple and reliable cytogenetic test for Fanconi's anemia (FA) that is based on the hypersensitivity of FA cells to mitomycin C (MC) is described. Equal volumes of whole blood from a patient in whom the diagnosis of FA is suspected and from a normal person of the opposite sex are co-cultured in phytohemagglutinin-co...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated (NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-01-479188
更新日期:2013-07-04 00:00:00
abstract::In this issue of Blood, the findings of Chakraborty et al and Emile et al support a model in which the mitogen-activated protein kinase (MAPK) and PI3K/AKT pathways are critical in the pathogenesis of 2 of the most common histiocytoses—Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD)—whereas their...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2014-09-597765
更新日期:2014-11-06 00:00:00
abstract::Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subs...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2525
更新日期:2004-03-01 00:00:00
abstract::Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Managem...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-07-584664
更新日期:2015-07-09 00:00:00
abstract::The abnormal adherence of red blood cells (RBC to the blood vessel wall is believed to contribute to the vascular occlusion observed in patients with sickle call anemia. The cell adhesion receptors GPIV (CD36) and integrin alpha 4 beta 1 (CD49d/CD29) were previously identified on circulating sickle reticulocytes, and ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::Activation of human normal serum with tetanus/antitetanus immune complexes (TAT-IC) resulted in increased binding of 125I-labeled interleukin-1 beta (IL-1 beta) to serum factors, as opposed to untreated serum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography showed label...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-06-15 00:00:00
abstract::LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::Activation of sialic-acid-binding immunoglobulin-like lectin-G (Siglec-G) by noninfectious damage-associated molecular patterns controls innate immune responses. However, whether it also regulates T-cell-mediated adaptive immune responses is not known. Graft-versus-host reaction is a robust adaptive immune response ca...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-12-545335
更新日期:2014-05-29 00:00:00
abstract::In adult bone marrow, mature erythroblasts are produced within structures called erythroblastic islands and then cross the endothelial barrier to reach circulation. Erythroblastic islands are composed of a central macrophage surrounded by maturing erythroblasts. In this study, it is shown that erythroid cells, but not...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.7.1968
更新日期:2001-04-01 00:00:00
abstract::Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial alphavbeta3 integrin. To determine the contribution of LW activation...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-11-056101
更新日期:2007-10-01 00:00:00
abstract::Mammalian 15-lipoxygenases, which have been implicated in the differentiation of hematopoietic cells are commonly regarded as cytosolic enzymes. Studying the interaction of the purified rabbit reticulocyte 15-lipoxygenase with various types of biomembranes, we found that the enzyme binds to biomembranes when calcium i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2002-11-3547
更新日期:2003-05-15 00:00:00
abstract::We studied the relationship between the production of the 23-Kd interleukin-1 receptor antagonist (IL-1ra) and IL-1 beta in cultures of human peripheral blood mononuclear cells (PBMC) using a specific radioimmunoassay for IL-1ra that had a sensitivity of 166 +/- 11 pg/mL. PBMC cultured without human serum made little ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19(+) B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring re...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-08-665547
更新日期:2016-05-19 00:00:00
abstract::Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications me...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-1986
更新日期:2004-12-15 00:00:00
abstract::Human plasma fibrinogen is produced by liver parenchymal cells. Such molecules contain two classes of gamma-chains (gamma A, gamma'), which differ with respect to their COOH-terminal sequences. When fibrin is crosslinked in the presence of factor XIIIa and Ca2+, three types of gamma-dimer are formed (gamma A-gamma A; ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Marrow cells of myeloid lineage from 115 patients with myelodysplastic syndrome (MDS) were characterized by multidimensional flow cytometry and compared with findings in 104 patients with various disorders and 25 healthy donors. Based on phenotypic and scatter characteristics, a flow cytometric scoring system (FCSS) w...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-09-2768
更新日期:2003-07-01 00:00:00
abstract::Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic mal...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2005-04-1614
更新日期:2005-11-01 00:00:00
abstract::Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-05-716720
更新日期:2016-11-17 00:00:00
abstract::Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth facto...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-09-242180
更新日期:2010-01-07 00:00:00
abstract::Stem cell factor (SCF) and interleukin-3 (IL-3) both act on several target hematopoietic populations, including mast cells. We have isolated a unique murine mast cell line, B6M, that is phenotypically similar to immature mast cells. For B6M cells, IL-3 is a survival factor and alone does not stimulate proliferation. S...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 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