Abstract:
:Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders characterized by an increased incidence of thrombo-hemorrhagic complications. The acquired somatic Janus kinase 2 (JAK2) V617F mutation is present in the majority of PV and ET patients. Because aberrant protein Tyr-phosphorylation has been associated with hematopoietic malignancies, the activity of the tyrosine kinases Src and JAK2 was analyzed in resting and thrombin-stimulated platelets from 13 PV and 42 ET patients. JAK2 was found inactive in healthy and pathological resting cells regardless of the V617F mutation. In addition, Src was inactive in all resting platelets, but in the pathological specimens it was present in a preactivated conformation as a consequence of anomalous dephosphorylation of its inhibitory phospho-Tyr527 residue, likely mediated by Src homology-2 domain-containing protein Tyr-phosphatase-2 (SHP-2), whose constitutive activity correlated with its recruitment to Src. Low thrombin concentration triggered a more rapid Src-signaling activation, higher [Ca(2+)](c) increase, and aggregation in pathological platelets compared with controls. Thrombin-induced Src activation preceded JAK2 activation, which occurred simultaneously in normal and pathological platelets. Our results indicate that a constitutive Src kinase preactivation is implicated in platelet hypersensitivity and likely involved, at least partially, in the functional abnormalities of PV and ET platelets.
journal_name
Bloodjournal_title
Bloodauthors
Randi ML,Brunati AM,Scapin M,Frasson M,Deana R,Magrin E,Fabris F,Donella-Deana Adoi
10.1182/blood-2008-12-196535subject
Has Abstractpub_date
2010-01-21 00:00:00pages
667-76issue
3eissn
0006-4971issn
1528-0020pii
blood-2008-12-196535journal_volume
115pub_type
杂志文章相关文献
BLOOD文献大全abstract::Fas ligand (FasL) and perforin pathways not only are the major mechanisms of T cell-mediated cytotoxicity but also are involved in homeostatic regulation of these T cells. In the present study, we tested whether CD8+ donor T cells that are deficient in both perforin and FasL (cytotoxic double deficient [cdd]) could in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-08-3036
更新日期:2005-03-01 00:00:00
abstract::One of the functions of HLA class I alleles is interaction with natural killer (NK) cells. Receptors termed killer immunoglobulin-like receptors (KIRs) on NK cells recognize groups of HLA class I alleles, and interaction between receptor and class I allele inhibits reactivity of the NK cell. Failure to recognize the a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-04-1197
更新日期:2002-11-15 00:00:00
abstract::Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on a short hairpin RNA library and stromal cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-452003
更新日期:2013-03-28 00:00:00
abstract::Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal prolifera...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Recently, we have identified scavenger receptor class A member I (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of an FX reservoir at the macrophage surface. Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2 (PTX2). The presence of PTX2 is essential to ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-06-724351
更新日期:2017-04-27 00:00:00
abstract::Umbilical cord blood (UCB) is an attractive cell source for hematopoietic cell transplantation (HCT). Here we examine whether the combination of homeobox B4 (HOXB4) and Delta-1 ligand (DL) synergize when used together. Monkey and human UCB CD34(+) cells were transduced with a HOXB4-expressing gammaretroviral vector an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-286062
更新日期:2010-12-23 00:00:00
abstract::We have recently demonstrated that IgD(hi) B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgD(h...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-021089
更新日期:2007-03-15 00:00:00
abstract::The purpose of the present study was to evaluate the use of the variable regions of the T gamma rearranging gene of the second T cell receptor. Genomic DNA was extracted from leukemic cells of T and B precursor phenotypes and hybridized to probes that detect rearrangement of the V gamma regions. We present data showin...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperox...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.13.3505
更新日期:2001-12-15 00:00:00
abstract::Variations within proteasome β (PSMB) genes, which encode the β subunits of the 20S proteasome, may affect proteasome function, assembly, and/or binding of proteasome inhibitors. To investigate the potential association between PSMB gene variants and treatment-emergent resistance to bortezomib and/or long-term outcome...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2012-05-426924
更新日期:2012-11-29 00:00:00
abstract::To elucidate the biochemical basis of megaloblastic hematopoiesis, the cellular content and metabolism of deoxyribonucleoside triphosphates (dNTPs) were investigated using the bone marrow cells from nine patients with untreated vitamin B12 deficiency and one with folic acid deficiency. The marked imbalance among four ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-10-01 00:00:00
abstract::Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their delivery was optimized and they were targeted to short-lived proteins encoded by messenger RNA (mRNA) species with equally short half-lives. To test this hypothesis, an ODN targeted to the c-myb proto-oncogene was developed and used to purge m...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood.v99.4.1150
更新日期:2002-02-15 00:00:00
abstract::Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets am...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Graft-versus-host disease (GVHD), a life-threatening complication after allogeneic hematopoietic stem cell transplantation, is caused by alloreactive donor T cells that trigger host tissue damage. The inflammatory environment inside recipients is critical for GVHD pathogenesis, but the underpinning mechanisms remain e...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-281659
更新日期:2011-02-03 00:00:00
abstract::The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties wer...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::We previously found that the myeloid cell surface glycoprotein CD13 (gp150) is identical to aminopeptidase N (EC 3.4.11.2), a widely distributed membrane-bound, zinc-dependent metalloprotease with an extracellular enzymatic domain that cleaves N-terminal amino acid residues from oligopeptides (J Clin Invest 83:1299, 1...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-01-15 00:00:00
abstract::The metalloprotease ADAMTS13 is assumed to regulate the functional levels of von Willebrand factor (VWF) appropriate for normal hemostasis in vivo by reducing VWF multimer size, which directly represents the thrombogenic activity of this factor. Using an in vitro perfusion chamber system, we studied the mechanisms of ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-110700
更新日期:2008-02-01 00:00:00
abstract::Type I interferon (IFNalpha/beta) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNalpha/beta plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNalpha/beta in HIV-1 infectio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-11-190231
更新日期:2009-05-28 00:00:00
abstract::Most anticancer chemotherapies are immunosuppressive and induce nonimmunogenic tumor cell death. Bortezomib, a specific inhibitor of 26S proteasome, has shown clinical activity in several human tumors, including myeloma. Here we show that the uptake of human myeloma cells by dendritic cells (DCs) after tumor cell deat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-054221
更新日期:2007-06-01 00:00:00
abstract::Hematopoietic stem cells (HSC) transplanted in utero are in competition with endogenous HSC; thus, ultimately the graft constitutes a relatively small fraction of total HSC pool. To enhance the engraftment of donor cells in sheep fetuses, we preincubated these cells, ex vivo, for 16 hours at 37 degrees C with the cond...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is etiologically linked to Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease. Vascular endothelial growth factor-A (VEGF-A) is one of the essential factors required in KSHV pathogenesis, mainly due to its abil...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-09-3683
更新日期:2005-06-01 00:00:00
abstract::Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently, an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed in murine studies with constitutive depletion of DCs, as well as in patients with congenital...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-05-850321
更新日期:2019-01-24 00:00:00
abstract::In neutrophils, the phosphoinositide 3-kinase/Akt signaling cascade is involved in migration, degranulation, and O(2)(-) production. However, it is unclear whether the Akt kinase isoforms have distinct functions in neutrophil activation. Here we report functional differences between the 2 major Akt isoforms in neutrop...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-11-255323
更新日期:2010-05-27 00:00:00
abstract::Congenital thrombocytopenia may occur in isolation or accompanied by eczema and immunodeficiency, as part of the X-linked hereditary Wiskott-Aldrich syndrome (WAS). Because the clinical and immunologic picture of WAS is variable, particularly early in life, definite diagnosis cannot always be made in cases with a nega...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-06-15 00:00:00
abstract::Omenn syndrome (OS) is an inherited disorder characterized by an absence of circulating B cells and an infiltration of the skin and the intestine by activated oligoclonal T lymphocytes, indicating that a profound defect in the lymphoid developmental program could be accountable for this condition. Inherited mutations ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.9.2772
更新日期:2001-05-01 00:00:00
abstract::The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-396648
更新日期:2012-08-02 00:00:00
abstract::The EEN (extra eleven nineteen) gene, located on chromosome 19p13, was cloned as a fusion with MLL from a patient with acute myeloid leukemia (AML) with translocation t(11;19)(q23;p13). In this study, we characterized the genomic structure of the EEN gene, including its 5' regulatory region and transcription start sit...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-02-003517
更新日期:2007-01-15 00:00:00
abstract::Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in ET and PV patients previously treated with...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood.2019000428
更新日期:2019-10-31 00:00:00
abstract::Antithymocyte globulin (ATG) has recently been popularized as an effective treatment in myelodysplastic syndrome (MDS). We treated 8 anemic MDS patients (refractory anemia [RA] and refractory anemia with excess blasts [RAEB-1]) with ATG (40 mg/kg/d for 4 days) and prednisone in a phase 2 trial. The study was stopped e...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2002-09-2867
更新日期:2003-03-15 00:00:00