Abstract:
:Normal human erythroid cell maturation requests the transcription factor GATA-1 and a transient activation of caspase-3, with GATA-1 being protected from caspase-3-mediated cleavage by interaction with the chaperone heat shock protein 70 (Hsp70) in the nucleus. Erythroid cell dysplasia observed in early myelodysplastic syndromes (MDS) involves impairment of differentiation and excess of apoptosis with a burst of caspase activation. Analysis of gene expression in MDS erythroblasts obtained by ex vivo cultures demonstrates the down-regulation of a set of GATA-1 transcriptional target genes, including GYPA that encodes glycophorin A (GPA), and the up-regulation of members of the HSP70 family. GATA-1 protein expression is decreased in MDS erythroblasts, but restores in the presence of a pan-caspase inhibitor. Expression of a mutated GATA-1 that cannot be cleaved by caspase-3 rescues the transcription of GATA-1 targets, and the erythroid differentiation, but does not improve survival. Hsp70 fails to protect GATA-1 from caspases because the protein does not accumulate in the nucleus with active caspase-3. Expression of a nucleus-targeted mutant of Hsp70 protects GATA-1 and rescues MDS erythroid cell differentiation. Alteration of Hsp70 cytosolic-nuclear shuttling is a major feature of MDS that favors GATA-1 cleavage and differentiation impairment, but not apoptosis, in dysplastic erythroblasts.
journal_name
Bloodjournal_title
Bloodauthors
Frisan E,Vandekerckhove J,de Thonel A,Pierre-Eugène C,Sternberg A,Arlet JB,Floquet C,Gyan E,Kosmider O,Dreyfus F,Gabet AS,Courtois G,Vyas P,Ribeil JA,Zermati Y,Lacombe C,Mayeux P,Solary E,Garrido C,Hermine O,Fontedoi
10.1182/blood-2011-03-343475subject
Has Abstractpub_date
2012-02-09 00:00:00pages
1532-42issue
6eissn
0006-4971issn
1528-0020pii
blood-2011-03-343475journal_volume
119pub_type
杂志文章相关文献
BLOOD文献大全abstract::The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-11-467191
更新日期:2013-07-18 00:00:00
abstract::We prepared a heterohybrid cell line that secretes a human IgM monoclonal autoantibody that recognizes an antigen found on thrombin-activated or stored platelets. The surface expression of the epitope recognized by this autoantibody, 5E5, increases with time as platelets age in vitro, suggesting that it may represent ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Hydroxyurea, interferon, and HLA-identical sibling bone marrow transplantation are common therapies for chronic myelogenous leukemia (CML) in chronic phase. Which is best is controversial. The purpose of this study was to compare survival of patients with CML receiving HLA-identical sibling transplants versus hydroxyu...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-03-01 00:00:00
abstract::Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-235598
更新日期:2010-01-14 00:00:00
abstract::Custom-made monoclonal anti-idiotype antibodies (anti-Id MoAbs) have been tested as a treatment modality in 34 non-Hodgkin's lymphoma (NHL) patients. Partial or complete tumor remissions have been induced with this treatment in 68% of these patients. One mechanism by which anti-idiotype antibodies may have induced the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-02-15 00:00:00
abstract::Hepcidin is a 25-amino-acid peptide demonstrated to be the iron regulatory hormone capable of blocking iron absorption from the duodenum and iron release from macrophages. Mutations affecting hepcidin regulators or the hepcidin gene itself cause hemochromatosis, a common genetic disorder. Hepcidin is produced mainly b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-01-550467
更新日期:2014-06-05 00:00:00
abstract::Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of the cell cycle (G(1)MTC) for which little is known. The present study shows that the G(1)MTC is intact in activated T lymphocytes from mice with the p21(wa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.5.1505
更新日期:2001-03-01 00:00:00
abstract::Serine proteinase inhibitors (serpins) play a vital regulatory role in a wide range of biological processes, and serpins from viruses have been implicated in pathogen evasion of the host defence system. For the first time, we report a functional serpin gene from nematodes that may function in this manner. This gene, n...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-08-15 00:00:00
abstract::During the early period following bone marrow transplantation before the immune system has reached full functional maturity, unprimed, nonspecific lytic systems may play a critical role as antiviral or antitumor effectors. The reconstitution of cells with this potential is of particular importance in recipients of bon...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Survival in infants younger than 1 year who have acute lymphoblastic leukemia (ALL) is inferior whether MLL is rearranged (R) or germline (G). MLL translocations confer chemotherapy resistance, and infants experience excess complications. We characterized in vitro sensitivity to the pan-antiapoptotic BCL-2 family inhi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-04-425033
更新日期:2013-04-04 00:00:00
abstract::The pathophysiology of microthrombocytopenia in the Wiskott-Aldrich syndrome (WAS) and its milder form, X-linked thrombocytopenia (XLT), is unclear. Although quantitative defects are correctable by splenectomy, residual platelet abnormalities are suggestive of intrinsic disturbances of production. In contrast to human...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-03-1219
更新日期:2006-07-01 00:00:00
abstract::Caveolin-1 (Cav-1) is a key organizer of membrane specializations and a scaffold protein that regulates signaling in multiple cell types. We found increased Cav-1 expression in human and murine T cells after allogeneic hematopoietic cell transplantation. Indeed, Cav-1(-/-)donor T cells caused less severe acute graft-v...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-09-672428
更新日期:2016-04-14 00:00:00
abstract::Interleukin-3 (IL-3) is exclusively expressed by activated T and natural killer cells, a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner. We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-02-15 00:00:00
abstract::Between February 1986 and March 1990, 56 patients with relapsed Hodgkin's disease treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) received an autologous peripheral stem cell transplantation (PSCT) rather than an autologous bone marrow transplantation (ABMT) because each patient had a marrow ab...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of suc...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S progression, and whose activity is, in part, regulated through interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation resulting in deregulated cyclin D1. We previously showed ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0263
更新日期:2003-04-15 00:00:00
abstract::Inflammatory responses represent a hallmark of numerous pathologies including sepsis, bacterial infection, insulin resistance, and malign obesity. Here we describe an unexpected coactivator function for the nuclear receptor interacting protein 140 (RIP140) for nuclear factor kappaB (NFkappaB), a master transcriptional...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-11-121699
更新日期:2008-07-15 00:00:00
abstract::In this issue of Blood, Sehgal et al report on the clinical and pharmacodynamics analysis of pomalidomide dosing strategies in multiple myeloma (MM) and their impact on immune activation and cereblon targets. The particular novelty of this study lies in the direct correlation of immune effects triggered by pomalidomid...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-05-641746
更新日期:2015-06-25 00:00:00
abstract::Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 x 10(9)/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stim...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1995-03-01 00:00:00
abstract::The bcr-abl chimeric messenger RNA is frequently detected in chronic myeloid leukemia (CML) patients after bone marrow transplantation. It was previously reported that the relapse risk of bcr-abl detection 6 to 12 months after transplantation was greater than 40%. This risk decreased as the time between transplantatio...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood.v98.6.1701
更新日期:2001-09-15 00:00:00
abstract::Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) are synthetic ODNs with unmethylated DNA sequences that mimic viral and bacterial DNA and protect against infectious agents and tumor challenge. We show that CpG ODNs markedly accelerated graft-versus-host disease (GVHD) lethality by Toll-like receptor...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-113670
更新日期:2008-10-15 00:00:00
abstract::Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiat...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-05-15 00:00:00
abstract::Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis,...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Hematopoietic stem and progenitor cells were previously found to express Toll-like receptors (TLRs), suggesting that bacterial/viral products may influence blood cell formation. We now show that common lymphoid progenitors (CLPs) from mice with active HSV-1 infection are biased to dendritic cell (DC) differentiation, ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-04-151506
更新日期:2008-11-01 00:00:00
abstract::In lymphatic tissues, chronic lymphocytic leukemia (CLL) cells are interspersed with CD68(+) nurselike cells (NLCs), T cells, and other stromal cells that constitute the leukemia microenvironment. However, the mechanism regulating colocalization of CLL and these accessory cells are largely unknown. To dissect the mole...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-07-170415
更新日期:2009-03-26 00:00:00
abstract::Human natural killer (NK) cells express Toll-like receptor 9 (TLR9) transcript and, upon exposure to microbial CpG oligodeoxynucleotide (ODN), release cytokines and kill target cells. Here we show that NK cell treatment with CpG ODN results in down-modulation of KIR3DL2 inhibitory receptor from the cell surface and in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-256586
更新日期:2010-09-09 00:00:00
abstract::In this issue of Blood, Rollin et al demonstrate that heparin-induced thrombocytopenia and thrombosis (HIT) patients homozygous for arginine (R) at position 131 in the immunoglobulin (Ig)G receptor FcγRIIA have a significantly higher incidence of thrombosis, and show that plasma IgG may play a key role in modulating t...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-02-629782
更新日期:2015-04-09 00:00:00
abstract::We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00