当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia.

Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia.

Abstract：

:Human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia (ATL), a fatal T-cell leukemia resistant to chemotherapy, after more than 50 years of clinical latency from transmission through breast-feeding. Polyclonal expansion of virus-infected T cells predisposes them to transformation. Constitutive activation of nuclear factor-kappaB (NF-kappaB) in the leukemic cells is essential for their growth and survival. Blocking NF-kappaB has been shown to be a potential strategy to treat ATL. We tested this approach using a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), and also examined its application to chemoprevention by selective purging of the HTLV-1-infected cells. DHMEQ inhibited NF-kappaB activation in primary ATL cells and cell lines derived from them and induced apoptotic cell death. NF-kappaB inhibition down-regulated expression of genes involved in antiapoptosis or cell-cycle progression. DHMEQ protected severe combined immunodeficiency (SCID) mice inoculated with HTLV-1-transformed cells from death. In addition, DHMEQ selectively targeted HTLV-1-infected cells in the peripheral blood of virus carriers in vitro, resulting in a decreased number of infected cells. We conclude that NF-kappaB is a potential molecular target for treatment and prevention of ATL. As a potent NF-kappaB inhibitor, DHMEQ is a promising compound allowing the translation of this strategy into clinical medicine.

journal_name

Blood

journal_title

Blood

authors

Watanabe M,Ohsugi T,Shoda M,Ishida T,Aizawa S,Maruyama-Nagai M,Utsunomiya A,Koga S,Yamada Y,Kamihira S,Okayama A,Kikuchi H,Uozumi K,Yamaguchi K,Higashihara M,Umezawa K,Watanabe T,Horie R

doi

10.1182/blood-2004-09-3646

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

2462-71

issue

7

eissn

0006-4971

issn

1528-0020

pii

2004-09-3646

journal_volume

106

pub_type

杂志文章

相关文献

BLOOD文献大全
  • An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation.

    abstract：:An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion-binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody wa...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Arnaud E,Lafay M,Gaussem P,Picard V,Jandrot-Perrus M,Aiach M,Rendu F

    更新日期：1994-09-15 00:00:00

  • Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition.

    abstract：:C-abl oncogene 1, nonreceptor tyrosine kinase (ABL1) kinase inhibitors such as imatinib mesylate (imatinib) are effective in managing chronic myeloid leukemia (CML) but incapable of eliminating leukemia stem cells (LSCs), suggesting that kinase-independent pathways support LSC survival. Given that the bone marrow (BM)...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2013-07-511907

    authors： Ng KP,Manjeri A,Lee KL,Huang W,Tan SY,Chuah CT,Poellinger L,Ong ST

    更新日期：2014-05-22 00:00:00

  • Janus kinase inhibition by ruxolitinib extends dasatinib- and dexamethasone-induced remissions in a mouse model of Ph+ ALL.

    abstract：:Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is initiated and driven by the oncogenic fusion protein BCR-ABL, a constitutively active tyrosine kinase. Despite major advances in the treatment of this highly aggressive disease with potent inhibitors of the BCR-ABL kinase such as dasatinib, pat...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2014-09-601062

    authors： Appelmann I,Rillahan CD,de Stanchina E,Carbonetti G,Chen C,Lowe SW,Sherr CJ

    更新日期：2015-02-26 00:00:00

  • Hormonal effects on cell proliferation in a human erythroleukemia cell line (K562).

    abstract：:We have investigated the hormonal responsiveness of K562 cells using a serum-substituted in vitro clonogenic assay. Dexamethasone inhibited colony formation by the K562 cells, and the inhibitory effect could be reversed by progesterone (10(-6) M). Fluoxymesterone caused a prominent enhancement of K562 colony growth, w...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Gauwerky C,Golde DW

    更新日期：1980-11-01 00:00:00

  • The gene for the alpha 4 subunit of the VLA-4 integrin maps to chromosome 2Q31-32.

    abstract：:The VLA-4 integrin (CD49d/CD29), initially discovered on lymphoid cells, is actually known to be highly expressed on T cells, B cells, monocytes, and derived cell lines. Unlike other VLA integrins, mainly involved in cell-matrix adhesive interactions, VLA-4 has also been implicated in several cellular interactions. Ba...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Zhang ZH,Vekemans S,Aly MS,Jaspers M,Marynen P,Cassiman JJ

    更新日期：1991-11-01 00:00:00

  • A case-control study to assess the risk of immune thrombocytopenia associated with vaccines.

    abstract：:The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hem...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1182/blood-2012-05-431098

    authors： Grimaldi-Bensouda L,Michel M,Aubrun E,Leighton P,Viallard JF,Adoue D,Magy-Bertrand N,Tisserand G,Khellaf M,Durand JM,Quittet P,Fain O,Bonnotte B,Morin AS,Limal N,Costedoat-Chalumeau N,Morel N,Pan-Petesch B,Decaux O,

    更新日期：2012-12-13 00:00:00

  • The small 11 kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells.

    abstract：:Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5 kDa, 11 kDa, and NS1, for their funct...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2009-04-215756

    authors： Chen AY,Zhang EY,Guan W,Cheng F,Kleiboeker S,Yankee TM,Qiu J

    更新日期：2010-02-04 00:00:00

  • Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor eliminates acute myeloid leukemia cells with the potential to initiate leukemia in immunodeficient mice, but spares normal hemopoietic stem cells.

    abstract：:We studied the cell kill induced by granulocyte-macrophage colony-stimulating factor (GM-CSF ) fused to Diphtheria Toxin (DT-GM-CSF ) in acute myeloid leukemia (AML) samples and in populations of normal primitive hemopoietic progenitor cells. AML samples from three patients were incubated in vitro with 100 ng/mL DT-GM...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Terpstra W,Rozemuller H,Breems DA,Rombouts EJ,Prins A,FitzGerald DJ,Kreitman RJ,Wielenga JJ,Ploemacher RE,Löwenberg B,Hagenbeek A,Martens AC

    更新日期：1997-11-01 00:00:00

  • Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.

    abstract：:The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL-1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD-1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the a...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Rimokh R,Berger F,Delsol G,Charrin C,Berthéas MF,Ffrench M,Garoscio M,Felman P,Coiffier B,Bryon PA

    更新日期：1993-06-01 00:00:00

  • Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome.

    abstract：:We examined the prevalence and prognostic relevance of bone marrow reticulin fibrosis in 526 patients with World Health Organization-defined polycythemia vera evaluated at the time of initial diagnosis. Seventy-four patients (14%) displayed mostly grade 1 reticulin fibrosis, with only 2 cases showing higher-grade fibr...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究

    doi：10.1182/blood-2011-11-393819

    authors： Barbui T,Thiele J,Passamonti F,Rumi E,Boveri E,Randi ML,Bertozzi I,Marino F,Vannucchi AM,Pieri L,Rotunno G,Gisslinger H,Gisslinger B,Müllauer L,Finazzi G,Carobbio A,Gianatti A,Ruggeri M,Nichele I,D'Amore E,Rambald

    更新日期：2012-03-08 00:00:00

  • The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis.

    abstract：:Glucose is a major source of energy for living organisms, and its transport in vertebrates is a universally conserved property. Of all cell lineages, human erythrocytes express the highest level of the Glut1 glucose transporter with more than 200,000 molecules per cell. However, we recently reported that erythrocyte G...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2008-05-159269

    authors： Montel-Hagen A,Blanc L,Boyer-Clavel M,Jacquet C,Vidal M,Sitbon M,Taylor N

    更新日期：2008-12-01 00:00:00

  • Demonstration of reversible priming of human neutrophils using platelet-activating factor.

    abstract：:Exposure of neutrophils to agents such as lipopolysaccharide, tumor necrosis factor-alpha (TNF-alpha), and the granulocyte-macrophage colony-stimulating factor causes a major upregulation of subsequent agonist-induced NADPH oxidase activation. This priming effect is a prerequisite for neutrophil-mediated tissue damage...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Kitchen E,Rossi AG,Condliffe AM,Haslett C,Chilvers ER

    更新日期：1996-12-01 00:00:00

  • Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas.

    abstract：:Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase 1, open-label, dose-escalating trial of repeated intratumoral administration of TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and m...

    journal_title：Blood

    pub_type： 临床试验,杂志文章

    doi：10.1182/blood-2004-01-0360

    authors： Dummer R,Hassel JC,Fellenberg F,Eichmüller S,Maier T,Slos P,Acres B,Bleuzen P,Bataille V,Squiban P,Burg G,Urosevic M

    更新日期：2004-09-15 00:00:00

  • Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1.

    abstract：:The binding of neutrophil beta2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutroph...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Neelamegham S,Taylor AD,Burns AR,Smith CW,Simon SI

    更新日期：1998-09-01 00:00:00

  • Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states.

    abstract：:Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2006-03-013334

    authors： Krispin A,Bledi Y,Atallah M,Trahtemberg U,Verbovetski I,Nahari E,Zelig O,Linial M,Mevorach D

    更新日期：2006-11-15 00:00:00

  • The hematopoietic stem cell niche in homeostasis and disease.

    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

    authors： Calvi LM,Link DC

    更新日期：2015-11-26 00:00:00

  • Transforming growth factor-beta regulates c-kit message stability and cell-surface protein expression in hematopoietic progenitors.

    abstract：:The cell-surface receptor c-kit and its cognate ligand stem-cell factor (SCF) or steel factor (SLF) are important for the maintenance of hematopoiesis both in vitro and in vivo. Transforming growth factor-beta (TGF-beta) has been shown to be a potent inhibitor of SLF-mediated synergistic growth of murine Lin-Sca-1+ pr...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Dubois CM,Ruscetti FW,Stankova J,Keller JR

    更新日期：1994-06-01 00:00:00

  • Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR.

    abstract：:Myeloid leukemias in AKXD23 mice contain proviral insertions at Evi1, resulting in transcriptional activation. Although Evi1 is clearly involved in leukemia, gene transfer studies in mice with Evi1 fail to cause leukemia, arguing that cooperating events are necessary. We reanalyzed AKXD-23 tumors for cooperating provi...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-05-1626

    authors： Boyd KE,Xiao YY,Fan K,Poholek A,Copeland NG,Jenkins NA,Perkins AS

    更新日期：2006-01-15 00:00:00

  • Heavy and light chain primary structures control IgG3 nephritogenicity in an experimental model for cryocrystalglobulinemia.

    abstract：:Crystal formation by monoclonal immunoglobulins is a well-known but rare complication of B-cell neoplasia. We have designed an in vivo model of cryocrystalglobulinemia by grafting to mice hybridoma clones producing a pathogenic monoclonal immunogloblulin (Ig) G3kappa. One clone, 8A4, secreted a singular IgG3 that form...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Rengers JU,Touchard G,Decourt C,Deret S,Michel H,Cogné M

    更新日期：2000-06-01 00:00:00

  • Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase.

    abstract：:Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a multistep, highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, tube differentiation, and survival. Eicosanoids, arachidonic acid (AA)-derived metabolites, have potent biologic activities o...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Nie D,Tang K,Diglio C,Honn KV

    更新日期：2000-04-01 00:00:00

  • The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development.

    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

    authors： Wu L,Maillard I,Nakamura M,Pear WS,Griffin JD

    更新日期：2007-11-15 00:00:00

  • Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum.

    abstract：:Intracellular protein transport in endothelial cells is selectively inhibited by homocysteine, a thiol amino acid associated with both thrombosis and atherosclerosis. In a previous study, homocysteine decreased cell surface expression of the surface transmembrane glycoprotein thrombomodulin without decreasing secretio...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Lentz SR,Sadler JE

    更新日期：1993-02-01 00:00:00

  • Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia.

    abstract：:Aberrant expression of Aurora kinases and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML), and preclinical data for inhibition of Aurora kinases or Mdm2 are promising. However, it remains largely unknown whether the viability of cells exposed to Au...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2008-01-128611

    authors： Kojima K,Konopleva M,Tsao T,Nakakuma H,Andreeff M

    更新日期：2008-10-01 00:00:00

  • Relation of autonomous and interleukin-2-responsive growth of leukemic cells to survival in adult T-cell leukemia.

    abstract：:We examined autonomous and interleukin-2 (IL-2)-responsive growth activities of leukemic cells derived from peripheral blood, as well as several clinical manifestations, including serum lactate dehydrogenase (LDH) level, of 35 patients with adult T-cell leukemia (ATL) to determine whether these properties were related...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Arima N,Hidaka S,Fujiwara H,Matsushita K,Ohtsubo H,Arimura K,Kukita T,Fukumori J,Tanaka H

    更新日期：1996-04-01 00:00:00

  • Targeted inhibition of PI3Kα/δ is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL.

    abstract：:Inhibition of the B-cell receptor (BCR) signaling pathway is a promising treatment strategy in multiple B-cell malignancies. However, the role of BCR blockade in diffuse large B-cell lymphoma (DLBCL) remains undefined. We recently characterized primary DLBCL subsets with distinct genetic bases for perturbed BCR/phosph...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2018-08-872465

    authors： Bojarczuk K,Wienand K,Ryan JA,Chen L,Villalobos-Ortiz M,Mandato E,Stachura J,Letai A,Lawton LN,Chapuy B,Shipp MA

    更新日期：2019-01-03 00:00:00

  • P-selectin glycoprotein ligand-1 is essential for adhesion to P-selectin but not E-selectin in stably transfected hematopoietic cell lines.

    abstract：:P-selectin (CD62P) is a member of the selectin family of adhesion molecules involved in the regulation of leukocyte traffic. P-selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like molecule that is thought to be a primary ligand for P-selectin. The interaction of P-selectin with PSGL-1 results in leukocyte rolling a...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Snapp KR,Wagers AJ,Craig R,Stoolman LM,Kansas GS

    更新日期：1997-02-01 00:00:00

  • CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection.

    abstract：:It has been suggested that human cytomegalovirus (HCMV) evades the immune system by infecting and paralyzing antigen-presenting cells. This view is based mainly on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy pe...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-05-2016

    authors： Kvale EØ,Dalgaard J,Lund-Johansen F,Rollag H,Farkas L,Midtvedt K,Jahnsen FL,Brinchmann JE,Olweus J

    更新日期：2006-03-01 00:00:00

  • Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression.

    abstract：:Elevated levels of interleukin 7 (IL-7) have been correlated with various T-cell depletion conditions, including HIV infection, and suggested as an indicator of HIV disease progression (AIDS and death). Here, the assessment of pathogenic simian immunodeficiency virus (SIVmac239) infection in rhesus macaques demonstrat...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-03-0874

    authors： Muthukumar A,Wozniakowski A,Gauduin MC,Paiardini M,McClure HM,Johnson RP,Silvestri G,Sodora DL

    更新日期：2004-02-01 00:00:00

  • Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications.

    abstract：:Recurrence of multiple myeloma (MM) after therapy suggests the presence of tumor-initiating subpopulations. In our study, we performed flow cytometry-based Hoechst 33342 staining to evaluate the existence of a MM population with stem-like features known as side population (SP) cells. SP cells exhibit substantial heter...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-02-267344

    authors： Jakubikova J,Adamia S,Kost-Alimova M,Klippel S,Cervi D,Daley JF,Cholujova D,Kong SY,Leiba M,Blotta S,Ooi M,Delmore J,Laubach J,Richardson PG,Sedlak J,Anderson KC,Mitsiades CS

    更新日期：2011-04-28 00:00:00

  • V(D)J recombinatorial repertoire diversification during intraclonal pro-B to B-cell differentiation.

    abstract：:The initial B-cell repertoire is generated by combinatorial immunoglobulin V(D)J gene segment rearrangements that occur in a preferential sequence. Because cellular proliferation occurs during the course of these rearrangement events, it has been proposed that intraclonal diversification occurs during this phase of B-...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2002-06-1828

    authors： Wang YH,Zhang Z,Burrows PD,Kubagawa H,Bridges SL Jr,Findley HW,Cooper MD

    更新日期：2003-02-01 00:00:00