Abstract:
:Ras-related C3 botulinum toxin substrate 2 (RAC2), through interactions with reduced NAD phosphate oxidase component p67 phox , activates neutrophil superoxide production, whereas interactions with p21-activated kinase are necessary for fMLF-induced actin remodeling. We identified 3 patients with de novo RAC2[E62K] mutations resulting in severe T- and B-cell lymphopenia, myeloid dysfunction, and recurrent respiratory infections. Neutrophils from RAC2[E62K] patients exhibited excessive superoxide production, impaired fMLF-directed chemotaxis, and abnormal macropinocytosis. Cell lines transfected with RAC2[E62K] displayed characteristics of active guanosine triphosphate (GTP)-bound RAC2 including enhanced superoxide production and increased membrane ruffling. Biochemical studies demonstrated that RAC2[E62K] retains intrinsic GTP hydrolysis; however, GTPase-activating protein failed to accelerate hydrolysis resulting in prolonged active GTP-bound RAC2. Rac2+/E62K mice phenocopy the T- and B-cell lymphopenia, increased neutrophil F-actin, and excessive superoxide production seen in patients. This gain-of-function mutation highlights a specific, nonredundant role for RAC2 in hematopoietic cells that discriminates RAC2 from the related, ubiquitous RAC1.
journal_name
Bloodjournal_title
Bloodauthors
Hsu AP,Donkó A,Arrington ME,Swamydas M,Fink D,Das A,Escobedo O,Bonagura V,Szabolcs P,Steinberg HN,Bergerson J,Skoskiewicz A,Makhija M,Davis J,Foruraghi L,Palmer C,Fuleihan RL,Church JA,Bhandoola A,Lionakis MS,Campdoi
10.1182/blood-2018-11-886028subject
Has Abstractpub_date
2019-05-02 00:00:00pages
1977-1988issue
18eissn
0006-4971issn
1528-0020pii
blood-2018-11-886028journal_volume
133pub_type
杂志文章相关文献
BLOOD文献大全abstract::As mouse models have become commonplace for studying hemostasis and thrombosis, we considered whether the mouse system had utility for assessing genetic alterations in platelet receptors. Platelets from 5 mouse strains (C57BL/6 [C57], FVB/N [FVB], BALB/c, C3H/He, and 129Sv) showed only minor differences in the express...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-10-3721
更新日期:2004-05-01 00:00:00
abstract::Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder of childhood, is distinct from adult-type chronic myelogenous leukemia (CML) and bears resemblance to chronic myelomonocytic leukemia (CMMoL). Since mutations in the N-ras gene have been found at high frequencies in CMMoL, but only rarely in C...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immuno...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-04-087775
更新日期:2007-12-15 00:00:00
abstract::Cumulative evidence indicates that MYC, one of the major downstream effectors of NOTCH1, is a critical component of T-cell acute lymphoblastic leukemia (T-ALL) oncogenesis and a potential candidate for targeted therapy. However, MYC is a complex oncogene, involving both fine protein dosage and cell-context dependency,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-336842
更新日期:2011-06-16 00:00:00
abstract::Interleukin-3 (IL-3) is a hematopoietic growth factor that regulates the differentiation of multilineage and committed progenitor cells and the functions of some mature blood cells. The expression of human IL-3 appears to be restricted to stimulated T lymphocytes. We have investigated the kinetics and mechanisms invol...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-03-15 00:00:00
abstract::Analysis of a growing number of chromosomal translocations in human tumors have shown that they frequently result in gene fusions encoding chimeric proteins. We have characterized the recurrent t(12;21)(p12;q22) translocation present in human B-lineage acute leukemias. This translocation fused two genes, tel and AML1,...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-06-15 00:00:00
abstract::Factor V Leiden (FVL) is associated with venous thrombosis; however, an association between FVL and arterial thrombosis remains controversial. We investigated FVL as a risk factor for myocardial infarction (MI), ischemic stroke (IS), or non-MI ischemic heart disease (non-MI-IHD). The design was 3 case-control studies ...
journal_title:Blood
pub_type: 杂志文章,meta分析
doi:10.1182/blood-2002-01-0111
更新日期:2002-07-01 00:00:00
abstract::We analyzed the expression of plasma glutathione peroxidase (GSHPx-P) messenger RNA (mRNA) in mouse, rat, and human tissues, using a human GSHPx-P cDNA clone as the probe. Unlike the classical cellular glutathione peroxidase (GSHPx-1), GSHPx-P expression appears to be tissue-specific. In the mouse and rat, kidney expr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-06-15 00:00:00
abstract::The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3(+) (CD141(+)) subset DCs may be particularly effective in DC vaccination trials. BDCA-3(+) DCs ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-434498
更新日期:2012-12-20 00:00:00
abstract::Signaling mediated by various Notch receptors and their ligands regulates diverse biological processes, including lymphoid cell fate decisions. Notch1 is required during T-cell development, while Notch2 and the Notch ligand Delta-like1 control marginal zone B (MZB) cell development. We previously determined that Maste...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-06-097030
更新日期:2007-11-15 00:00:00
abstract::Impaired fibrinolysis, resulting from increased plasminogen activator inhibitor-1 (PAI-1) or reduced tissue-type plasminogen activator (t-PA) plasma levels, may predispose the individual to subacute thrombosis in sepsis and inflammation. The objective of these studies was to show that adenovirus-mediated gene transfer...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-08-15 00:00:00
abstract::Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and u...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-02-005496
更新日期:2006-09-01 00:00:00
abstract::Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these incl...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract::We explored adeno-associated viral vector (AAV)-mediated gene transfer in the perinatal period in animal models of severe congenital factor VII (FVII) deficiency, a disease associated with early postnatal life-threatening hemorrhage. In young adult mice with plasma FVII < 1% of normal, a single tail vein administratio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-377630
更新日期:2012-01-26 00:00:00
abstract::The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangement...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Regulated by histone acetyltransferases and deacetylases (HDACs), histone acetylation is a key epigenetic mechanism controlling chromatin structure, DNA accessibility, and gene expression. HDAC inhibitors induce growth arrest, differentiation, and apoptosis of tumor cells and are used as anticancer agents. Here we des...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-284711
更新日期:2011-01-27 00:00:00
abstract::The c-Myb transcription factor controls differentiation and proliferation in hematopoietic and other cell types and has latent transforming activity, but little is known about its regulation during the cell cycle. Here, c-Myb was identified as part of a protein complex from human T cells containing the cyclin-dependen...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-08-3342
更新日期:2005-05-15 00:00:00
abstract::To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::In lymphocytes, the second messenger cyclic adenosine monophosphate (cAMP) plays a well-established antiproliferative role through inhibition of G(1)/S transition and S-phase progression. We have previously demonstrated that, during S-phase arrest, cAMP inhibits the action of S phase-specific cytotoxic compounds, lead...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-204883
更新日期:2009-07-16 00:00:00
abstract::Throughout its history, chronic myeloid leukemia (CML) has set precedents for cancer research and therapy. These range from the identification of the first specific chromosomal abnormality associated with cancer to the development of imatinib as a specific, targeted therapy for the disease. The successful development ...
journal_title:Blood
pub_type: 历史文章,杂志文章,评审
doi:10.1182/blood-2008-07-077958
更新日期:2008-12-15 00:00:00
abstract::Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)-lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte mot...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-286872
更新日期:2010-11-25 00:00:00
abstract::T(11;18)(q21;q21) is the most common structural abnormality in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) leading to the fusion of the apoptosis inhibitor-2 (API2) gene and the MALT lymphoma-associated translocation (MALT1) gene. In 2 patients with MALT lymphoma of th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-09-2963
更新日期:2003-03-15 00:00:00
abstract::Reversible interactions of glycoconjugates on leukocytes with P- and E-selectin on endothelial cells mediate tethering and rolling of leukocytes in inflamed vascular beds, the first step in their recruitment to sites of injury. Although selectin ligands on hematopoietic precursors have been identified, here we review ...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-07-343566
更新日期:2011-12-22 00:00:00
abstract::Incubation of human macrophages with endotoxin resulted in significantly enhanced colony-stimulating activity (CSA) production by these cells. Preincubation of endotoxin with mature granulocytes abolished this stimulatory effect. The stimulatory effect of endotoxin on macrophage CSA production was not abolished, howev...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1978-05-01 00:00:00
abstract::The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characteriz...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-06-723742
更新日期:2017-01-12 00:00:00
abstract::We previously showed that incorporating target sequences for the hematopoietic-specific microRNA miR-142 into an antigen-encoding transgene prevents antigen expression in antigen-presenting cells (APCs). To determine whether this approach induces immunologic tolerance, we treated mice with a miR-142-regulated lentivir...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-04-214569
更新日期:2009-12-10 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::Activation of endothelial cells, important in processes such as angiogenesis, is regulated by cell surface receptors, including those in the tyrosine kinase (RTK) family. Receptor activity, in turn, can be modulated by phosphorylation, turnover, or proteolytic release of a soluble extracellular domain. Previously, we ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-03-15 00:00:00
abstract::As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. In the present study, we report that NSC606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (AML) cells NB4 and U937 and inhib...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-10-4011
更新日期:2005-05-01 00:00:00