Abstract:
:Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense mutation replacing a lysine with an asparagine residue at position 201 (K201N) of STAT1. This mutation causes the abnormal splicing out of exon 8 from most STAT1 mRNAs, thereby decreasing (by ~ 70%) STAT1 protein levels. The mutant STAT1 proteins are not intrinsically deleterious, in terms of tyrosine phosphorylation, dephosphorylation, homodimerization into γ-activating factor and heterotrimerization into ISGF-3, binding to specific DNA elements, and activation of the transcription. Interestingly, the activation of γ-activating factor and ISGF3 was impaired only at early time points in the various cells from patient (within 1 hour of stimulation), whereas sustained impairment occurs in other known forms of complete and partial recessive STAT1 deficiency. Consequently, delayed responses were normal; however, the early induction of interferon-stimulated genes was selectively and severely impaired. Thus, the early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections.
journal_name
Bloodjournal_title
Bloodauthors
Kong XF,Ciancanelli M,Al-Hajjar S,Alsina L,Zumwalt T,Bustamante J,Feinberg J,Audry M,Prando C,Bryant V,Kreins A,Bogunovic D,Halwani R,Zhang XX,Abel L,Chaussabel D,Al-Muhsen S,Casanova JL,Boisson-Dupuis Sdoi
10.1182/blood-2010-04-280586subject
Has Abstractpub_date
2010-12-23 00:00:00pages
5895-906issue
26eissn
0006-4971issn
1528-0020pii
blood-2010-04-280586journal_volume
116pub_type
杂志文章相关文献
BLOOD文献大全abstract::The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-233445
更新日期:2010-01-28 00:00:00
abstract::CD4(+)CD25(+)FOXP3(+) regulatory T cells (CD4(+) Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2006-01-0177
更新日期:2006-07-15 00:00:00
abstract::Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020006441
更新日期:2020-09-09 00:00:00
abstract::A large number of alterations in genes encoding receptor tyrosine kinase (RTK), namely FLT3, c-KIT, platelet-derived growth factor (PDGF) receptors, fibroblast growth factor (FGF) receptors, and the anaplastic large cell lymphoma kinase (ALK), have been found in hematopoietic malignancies. They have drawn much attenti...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2010-04-279752
更新日期:2010-10-07 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
abstract::The measurement of platelet-associated IgG (PAIgG) is a potentially useful diagnostic test for idiopathic thrombocytopenia purpura (ITP). However, the restricted application of PAIgG measurements to thrombocytopenic populations primarily comprised of ITP patients will artificially enhance its diagnosis specificity. Fo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-10-01 00:00:00
abstract::This study tested the hypothesis that combination of antiangiogenic therapy and tumor immunotherapy of cancer is synergistic. To inhibit angiogenesis, mice were immunized with dendritic cells (DCs) transfected with mRNA that encode products that are preferentially expressed during neoangiogenesis: vascular endothelial...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-12-3738
更新日期:2003-08-01 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::We examined whether activated protein C (APC) reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting leukocyte activation. In a rat model, intravenous administration of APC markedly reduced I/R-induced renal dysfunction and histological changes, whereas intravenous administration of dansyl glutamylglycy...
journal_title:Blood
pub_type: 杂志文章,收录出版
doi:
更新日期:2000-06-15 00:00:00
abstract::Gimap4, a member of the newly identified GTPase of the immunity-associated protein family (Gimap), is strongly induced by the pre-T-cell receptor in precursor T lymphocytes, transiently shut off in double-positive thymocytes, and reappears after TCR-mediated positive selection. Here, we show that Gimap4 remains expres...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-4616
更新日期:2006-07-15 00:00:00
abstract::IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that res...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-08-172767
更新日期:2009-04-09 00:00:00
abstract::In an international collaborative study, a central histologic review identified 891 patients with essential thrombocythemia, strictly defined by World Health Organization criteria. After a median follow-up of 6.2 years, 109 (12%) patients experienced arterial (n = 79) or venous (n = 37) thrombosis. In multivariable an...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-02-339002
更新日期:2011-06-02 00:00:00
abstract::Cytotoxic T lymphocytes (CTLs) kill target cells through the polarized release of lytic molecules from secretory lysosomes. Loss of munc13-4 function inhibits this process and causes familial hemophagocytic lymphohistiocytosis type 3 (FHL3). munc13-4 binds rab27a, but the necessity of the complex remains enigmatic, be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-339523
更新日期:2011-08-11 00:00:00
abstract::Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cell...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::In mouse mid-gestational embryos, definitive hematopoietic stem progenitor cells are derived directly from a very small proportion of the arterial endothelium. However, the physiological mechanisms restraining excessive endothelial-hematopoietic transition remain elusive. We show here that genetic deletion of Smad4 fr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-09-526053
更新日期:2014-04-03 00:00:00
abstract::Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical and radiologic features are not well described. We reviewed data on cervical magnetic resonance angiography (cMRA) performed prospectively in 67 patients (55 ...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2011-03-337915
更新日期:2011-12-01 00:00:00
abstract::Hepcidin controls systemic iron availability, and its excess contributes to the anemia of chronic diseases, the most prevalent anemia in hospitalized patients. We previously reported that heparins are efficient hepcidin inhibitors both in vitro and in vivo, but their anticoagulant activity limits therapeutic use. We s...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-07-515221
更新日期:2014-03-06 00:00:00
abstract::We investigated the clinical activity of the farnesyl transferase inhibitor R115777 in 22 patients with chronic myelogenous leukemia (CML) in chronic, accelerated, or blastic phase and in 8 patients with myelofibrosis (MF) and 10 patients with multiple myeloma (MM). R115777 was administered at 600 mg orally twice dail...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2002-07-1973
更新日期:2003-03-01 00:00:00
abstract::Homologous recombination repair (HRR) protects cells from the lethal effect of spontaneous and therapy-induced DNA double-stand breaks. HRR usually depends on BRCA1/2-RAD51, and RAD52-RAD51 serves as back-up. To target HRR in tumor cells, a phenomenon called "synthetic lethality" was applied, which relies on the addic...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-501072
更新日期:2013-08-15 00:00:00
abstract::miRNAs have emerged as master regulators of cancer-related events. miRNA dysregulation also occurs in Kaposi sarcoma (KS). Exploring the roles of KS-associated miRNAs should help to identify novel angiogenesis and lymphangiogenesis pathways. In the present study, we show that Kaposi sarcoma-associated herpesvirus (KSH...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-01-330589
更新日期:2011-09-08 00:00:00
abstract::The large granular lymphocyte (LGL) population, which effects a natural killer (NK) function, consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Thrombin Metz and normal thrombin, resulting from activation of the respective prothrombins by factor Xa in the presence of calcium, phospholipid, and factor Va, were purified by chromatography on sulfopropyl Sephadex. By physicochemical criteria, thrombin Metz is identical to normal thrombin. Its functional propertie...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-343962
更新日期:2011-12-22 00:00:00
abstract::The genetic basis for Waldenström macroglobulinemia (WM) remains to be clarified. Although 6q losses are commonly present, recurring gene losses in this region remain to be defined. We therefore performed whole genome sequencing (WGS) in 30 WM patients, which included germline/tumor sequencing for 10 patients. Validat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-09-525808
更新日期:2014-03-13 00:00:00
abstract::Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoiet...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-316745
更新日期:2011-06-02 00:00:00
abstract::All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1999-06-15 00:00:00
abstract::Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity toward nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histo...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-06-790519
更新日期:2017-12-28 00:00:00
abstract::The bone marrow microenvironment contains a heterogeneous population of stromal cells organized into niches that support hematopoietic stem cells (HSCs) and other lineage-committed hematopoietic progenitors. The stem cell niche generates signals that regulate HSC self-renewal, quiescence, and differentiation. Here, we...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2015-07-533588
更新日期:2015-11-26 00:00:00
abstract::Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by excessive erythrocyte production. Most patients with PV harbor an activating JAK2 mutation, but the molecular links between this mutation and erythrocyte overproduction are unknown. The interaction between death receptors and their ligands...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-07-3037
更新日期:2006-05-01 00:00:00
abstract::Surface receptors specific for either the C4b (CR1) or C3d (CR2) component of complement were examined on the neoplastic cells from 30 cases of non-Hodgkin's lymphoma of B-cell origin and on cells derived from 9 normal lymphoid tissues. Lymphocyte suspensions from non-neoplastic peripheral blood, tonsils, and lymph no...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00