Abstract:
:Large granular lymphocyte (LGL) leukemia results from clonal expansion of CD3+ cytotoxic T lymphocytes or CD3- natural killer (NK) cells. Chronic antigen stimulation is postulated to promote long-term survival of LGL leukemia cells through constitutive activation of multiple survival pathways, resulting in global dysregulation of apoptosis and resistance to activation-induced cell death. We reported previously that nuclear factor κB (NF-κB) is a central regulator of the survival network for leukemic LGL. However, the mechanisms that trigger constitutive activation of NF-κB in LGL leukemia remain undefined. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in tumor cells but can also activate NF-κB through interaction with TRAIL receptors 1, 2, and 4 (also known as DR4, DR5, and DcR2, respectively). The role of TRAIL has not been studied in LGL leukemia. In this study, we hypothesized that TRAIL interaction with DcR2 contributes to NF-κB activation in LGL leukemia. We observed upregulated TRAIL messenger RNA and protein expression in LGL leukemia cells with elevated levels of soluble TRAIL protein in LGL leukemia patient sera. We also found that DcR2 is the predominant TRAIL receptor in LGL leukemia cells. We demonstrated that TRAIL-induced activation of DcR2 led to increased NF-κB activation in leukemic LGL. Conversely, interruption of TRAIL-DcR2 signaling led to decreased NF-κB activation. Finally, a potential therapeutic application of proteasome inhibitors (bortezomib and ixazomib), which are known to inhibit NF-κB, was identified through their ability to decrease proliferation and increase apoptosis in LGL leukemia cell lines and primary patient cells.
journal_name
Bloodjournal_title
Bloodauthors
Yang J,LeBlanc FR,Dighe SA,Hamele CE,Olson TL,Feith DJ,Loughran TP Jrdoi
10.1182/blood-2017-09-808816subject
Has Abstractpub_date
2018-06-21 00:00:00pages
2803-2815issue
25eissn
0006-4971issn
1528-0020pii
blood-2017-09-808816journal_volume
131pub_type
杂志文章相关文献
BLOOD文献大全abstract::Endothelial cells in vivo form the interface between the vascular and interstitial compartments and are strategically located to mediate vascular permeability and hemostasis. One mechanism endothelial cells use to maintain a nonthrombogenic surface is to polarize basement membrane constituents to the basolateral cell ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-06-15 00:00:00
abstract::It has been suggested that autotransplantation of splenic tissue following trauma may result in splenic implanta that protect the human host from severe infection with encapsulated bacteria. To test this hypothesis, Sprague-Dawley rats underwent sham operation, splenectomy, or splenectomy followed by autotransplantati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::The effect of both congenital and acquired factor VII deficiency on the cuticle bleeding time (CBT) was evaluated in dogs. The CBT has been previously documented to be a sensitive indicator of factor VIII:C deficiency in hemophilic dogs. Serial CBT determinations were made on normal dogs treated with high-dose warfari...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament remains poorly characterized. Here, we established E-cadherin (Cdh1) as a selective marker for IL-4/IL-13-exposed mouse and human macropha...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-05-221598
更新日期:2009-11-19 00:00:00
abstract::Recovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytoki...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2003-04-1200
更新日期:2004-05-15 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::T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature leukemia that occurs both in adults as a sporadic disease and in younger patients suffering an hereditary condition, ataxia telangiectasia (AT). The ATM gene, located in the 11q22-23 chromosomal region, is consistently mutated in AT patients. The strong p...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::T-cell depletion (TCD) of the donor marrow graft has been shown to reduce the severity of graft-versus-host disease (GVHD) in patients with chronic-phase (CP) chronic myelogenous leukemia (CML) undergoing HLA-identical sibling allogeneic marrow transplantation. However, there has been a corresponding reduction in the ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::The content of filamentous actin in individual platelets was measured by flow cytometry, using a fluorescent probe specific for filamentous actin (F-actin), 7-nitrobenz-2-oxa-1,3-phallacidin (NBD-phallacidin). NBD-phallacidin binding to fixed platelets was specific in that either pretreatment of platelets with unlabel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-02-15 00:00:00
abstract::Virtually all cases of childhood ALL have chromosomal abnormalities and half contain translocations, which are nearly equally divided between random and nonrandom rearrangements. Nonrandom chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation, and the specific ge...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:1990-10-15 00:00:00
abstract::Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I ...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2012-01-404368
更新日期:2012-05-31 00:00:00
abstract::The von Willebrand factor propeptide, vW AgII, has been shown to be required for the formation of vWF multimers and sorting of vWF to storage granules; whether these 2 processes are independent events has been unclear. Chimeric constructs of human and canine vWF were developed to further define these processes and to ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Eosinophils are involved in the inflammatory response seen in allergy and helminthic infestations. Eosinophils synthesize transforming growth factor-alpha (TGF-alpha), which may play a role in the development of the characteristic fibrosis seen in longstanding high eosinophilia. Using immunoelectron microscopic techni...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Measurement of plasma levels of two secreted platelet proteins (beta-thromboglobulin and platelet factor 4) has been suggested as a means for detecting increased platelet activation in vivo. A crucial question in the measurement is the distinction between in vivo and in vitro secretion of the proteins. One approach to...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:1981-02-01 00:00:00
abstract::Pretreatment of endothelial cells with cytokines enhances the adherence of leukocytes, a process that is mediated by surface proteins expressed on both cell types. A three-dimensional model system for the simultaneous determination of leukocyte adherence and migration was used to study the contribution of CD11/CD18, e...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-11-15 00:00:00
abstract::Mutations in human prothrombin that generate a stable form of meizothrombin or meizothrombin(desF1) cause dysprothrombinemia in both the homozygous and heterozygous state, suggesting that meizothrombin has dominant anticoagulant effects in vivo. The enzymatic characterization of recombinant mouse meizothrombin, meizot...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-02-0478
更新日期:2004-07-15 00:00:00
abstract::The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-380410
更新日期:2012-06-14 00:00:00
abstract::The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF-beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-11-15 00:00:00
abstract::Toll-like receptor 4 (TLR4) initiates both myeloid differentiation factor 88 (MyD88)-dependent and Toll/interleukin (IL)-1R domain-containing adapter, inducing interferon (IFN)-beta-dependent signaling, leading to production of proinflammatory mediators and type I interferon (IFN) to eliminate pathogens. However, unco...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-01-066027
更新日期:2007-08-01 00:00:00
abstract::Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and its human homologue GOS19.1/LD78 are members of the C-C chemokine/intercrine family of secreted proteins. They have proinflammatory properties and also inhibit cell cycle progression of hematopoietic stem cells. Characterization of MIP-1 alpha receptor(s) has b...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-09-15 00:00:00
abstract::Intracranial hemorrhage is the third most frequent cause of cerebrovascular disease, but few genetic risk factors have been associated with its development. Recently, it has been reported that some polymorphisms that affect clotting factors increase the risk for thrombosis. However, reports have analyzed the effect of...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.10.2979
更新日期:2001-05-15 00:00:00
abstract::Cytogenetic and histopathologic data were correlated with clinical parameters from 423 patients with non-Hodgkin's lymphoma (NHL). Clinical correlations were performed on subgroups of 149 patients with low-grade lymphoma (LG) and 205 patients with diffuse lymphoma with a large cell component (DLLC). Correlations were ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Transplant-associated thrombotic microangiopathy (TA-TMA) occurs frequently after hematopoietic stem cell transplantation (HSCT) and can lead to significant morbidity and mortality. There are no data addressing individual susceptibility to TA-TMA. We performed a hypothesis-driven analysis of 17 candidate genes known t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-08-663435
更新日期:2016-02-25 00:00:00
abstract::The primitive hematopoietic stem/progenitor cells (HSPCs) during embryonic hematopoiesis are thought to be short-lived (SL) with limited self-renewal potential. The fate and consequence of these short-lived HSPCs, once reprogrammed into "long-lived" in a living animal body, remain unknown. Here we show that targeted e...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-327908
更新日期:2011-10-06 00:00:00
abstract::Through its Src homology 3 (SH3) and SH2 domains, the Src kinase Lyn interacts with a small number of phosphoproteins, such as Shc, Cbl, and Vav, which regulate cell cycle and the cytoskeleton. Using Lyn's Unique, SH3, and SH2 domains as bait in a yeast 2-hybrid screen, we isolated a novel gene product with features o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-03-0851
更新日期:2003-04-01 00:00:00
abstract::Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymp...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-447375
更新日期:2013-09-19 00:00:00
abstract::Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-04-780106
更新日期:2017-11-30 00:00:00
abstract::The transcription factor KLF4 may act both as an oncogene and a tumor suppressor in a tissue-depending manner. In T- and pre-B-cell lymphoma, KLF4 was found to act as tumor suppressor. We found the KLF4 promoter methylated in B-cell lymphoma cell lines and in primary cases of B-cell lymphomas, namely, follicular lymph...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-256446
更新日期:2010-09-02 00:00:00
abstract::Eosinophils are important in antibody-mediated immune defense against parasites based on interaction with Ig receptors (FcR). Of the three classes of IgG FcR in humans, hFc gamma RI, II, and III, solely hFc gamma RII (CD32) is expressed on freshly isolated eosinophils. Despite an expression level similar to that found...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Inherited type 1 antithrombin (AT) deficiency is characterized by a reduction in both immunologically and functionally detectable protein. The disorder is associated with a high risk of thromboembolic disease. We have investigated the molecular basis of type 1 AT deficiency in three unrelated families. We have used th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00