当前位置： SCI文献检索 > BLOOD期刊下所有文献 > VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition.

VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition.

Abstract：

:Similar to endothelial cells (ECs), vascular endothelial growth factor (VEGF) induces Bcl-2 expression on VEGF receptor-positive (VEGFR(+)) primary leukemias and cell lines, promoting survival. We investigated the molecular pathways activated by VEGF on such leukemias, by performing a gene expression analysis of VEGF-treated and untreated HL-60 leukemic cells. One gene to increase after VEGF stimulation was heat shock protein 90 (Hsp90). This was subsequently confirmed at the protein level, on primary leukemias and leukemic cell lines. VEGF increased the expression of Hsp90 by interacting with KDR and activating the mitogen-activated protein kinase cascade. In turn, Hsp90 modulated Bcl-2 expression, as shown by a complete blockage of VEGF-induced Bcl-2 expression and binding to Hsp90 by the Hsp90-specific inhibitor geldanamycin (GA). GA also blocked the VEGF-induced Hsp90 binding to APAF-1 on leukemic cells, a mechanism shown to inhibit apoptosis. Notably, VEGF blocked the proapoptotic effects of GA, correlating with its effects at the molecular level. Earlier, we showed that in some leukemias, a VEGF/KDR autocrine loop is essential for cell survival, whereas here we identified the molecular correlates for such an effect. We also demonstrate that the generation of a VEGF/VEGFR autocrine loop on VEGFR(+) cells such as ECs, also protected them from apoptosis. Infection of ECs with adenovirus-expressing VEGF resulted in elevated Hsp90 levels, increased Bcl-2 expression, and resistance to serum-free or GA-induced apoptosis. In summary, we demonstrate that Hsp90 mediates antiapoptotic and survival-promoting effects of VEGF, which may contribute to the survival advantage of VEGFR(+) cells such as subsets of leukemias.

journal_name

Blood

journal_title

Blood

authors

Dias S,Shmelkov SV,Lam G,Rafii S

doi

10.1182/blood.v99.7.2532

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

2532-40

issue

7

eissn

0006-4971

issn

1528-0020

journal_volume

99

pub_type

杂志文章

相关文献

BLOOD文献大全
  • HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation.

    abstract：:Dendritic cells (DCs) are antigen-presenting cells with the capacity to prime naive T cells for efficient cellular responses against pathogens such as HIV-1. DCs are also susceptible to HIV-1 infection, which may impair their ability to induce immunity. Here, we examined the ability of HIV-1-infected, in vitro-derived...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-07-2314

    authors： Smed-Sörensen A,Loré K,Walther-Jallow L,Andersson J,Spetz AL

    更新日期：2004-11-01 00:00:00

  • The critical roles of platelet activation and reduced NO bioavailability in fatal pulmonary arterial hypertension in a murine hemolysis model.

    abstract：:Pulmonary arterial hypertension (PAH) is suspected to be a strong mortality determinant of hemolytic disorders. However, direct contribution of acute intravascular hemolysis to fatal PAH has not been investigated. The roles of nitric oxide (NO) insufficiency and platelet activation in hemolysis-associated fatal PAH ha...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-01-267112

    authors： Hu W,Jin R,Zhang J,You T,Peng Z,Ge X,Bronson RT,Halperin JA,Loscalzo J,Qin X

    更新日期：2010-09-02 00:00:00

  • Localization of ADAMTS13 to the stellate cells of human liver.

    abstract：:Although the chromosomal localization (9q34) of the gene encoding the human form of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) and its exclusive expression in the liver have been established, the cells that produce this enzyme are yet to be determined. We investigated the ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-01-0152

    authors： Uemura M,Tatsumi K,Matsumoto M,Fujimoto M,Matsuyama T,Ishikawa M,Iwamoto TA,Mori T,Wanaka A,Fukui H,Fujimura Y

    更新日期：2005-08-01 00:00:00

  • A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding.

    abstract：:Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and hetero...

    journal_title：Blood

    pub_type： 杂志文章,评审

    doi：10.1182/blood-2018-02-831982

    authors： Baaten CCFMJ,Meacham S,de Witt SM,Feijge MAH,Adams DJ,Akkerman JN,Cosemans JMEM,Grassi L,Jupe S,Kostadima M,Mattheij NJA,Prins MH,Ramirez-Solis R,Soehnlein O,Swieringa F,Weber C,White JK,Ouwehand WH,Heemskerk JWM

    更新日期：2018-12-13 00:00:00

  • Active amino acids of the Kell blood group protein and model of the ectodomain based on the structure of neutral endopeptidase 24.11.

    abstract：:In addition to its importance in transfusion, Kell protein is a member of the M13 family of zinc endopeptidases and functions as an endothelin-3-converting enzyme. To obtain information on the structure of Kell protein we built a model based on the crystal structure of the ectodomain of neutral endopeptidase 24.11 (NE...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-05-1564

    authors： Lee S,Debnath AK,Redman CM

    更新日期：2003-10-15 00:00:00

  • Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model.

    abstract：:Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with p...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2009-03-210070

    authors： Agrawal-Singh S,Koschmieder S,Gelsing S,Stocking C,Stehling M,Thiede C,Thoennissen NH,Köhler G,Valk PJ,Delwel R,Mills K,Bäumer N,Tickenbrock L,Hansen K,Berdel WE,Müller-Tidow C,Serve H

    更新日期：2010-06-03 00:00:00

  • Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities.

    abstract：:The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-09-307264

    authors： Perrot A,Luquet I,Pigneux A,Mugneret F,Delaunay J,Harousseau JL,Barin C,Cahn JY,Guardiola P,Himberlin C,Recher C,Vey N,Lioure B,Ojeda-Uribe M,Fegueux N,Berthou C,Randriamalala E,Béné MC,Ifrah N,Witz F,Groupe Ouest

    更新日期：2011-07-21 00:00:00

  • EKLF-driven PIT1 expression is critical for mouse erythroid maturation in vivo and in vitro.

    abstract：:The PIT1/SLC20A1 protein, a well-described sodium/phosphate cotransporter and retrovirus receptor, has been identified recently as a modular of proliferation and apoptosis in vitro. The targeted deletion of the PIT1 gene in mice revealed a lethal phenotype due to severe anemia attributed to defects in liver developmen...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2012-05-427302

    authors： Forand A,Beck L,Leroy C,Rousseau A,Boitez V,Cohen I,Courtois G,Hermine O,Friedlander G

    更新日期：2013-01-24 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

  • alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner.

    abstract：:To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and alpha2-null mice. Our findings reveal that the alpha2beta1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-06-094680

    authors： Zhang Z,Ramirez NE,Yankeelov TE,Li Z,Ford LE,Qi Y,Pozzi A,Zutter MM

    更新日期：2008-02-15 00:00:00

  • Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia.

    abstract：:To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2(V617F) mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet coun...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2008-04-153783

    authors： Carobbio A,Finazzi G,Antonioli E,Guglielmelli P,Vannucchi AM,Delaini F,Guerini V,Ruggeri M,Rodeghiero F,Rambaldi A,Barbui T

    更新日期：2008-10-15 00:00:00

  • Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors.

    abstract：:Distinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develo...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-02-0384

    authors： Palucka AK,Gatlin J,Blanck JP,Melkus MW,Clayton S,Ueno H,Kraus ET,Cravens P,Bennett L,Padgett-Thomas A,Marches F,Islas-Ohlmayer M,Garcia JV,Banchereau J

    更新日期：2003-11-01 00:00:00

  • Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex.

    abstract：:A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions an...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Boukerche H,Berthier-Vergnes O,Tabone E,Doré JF,Leung LL,McGregor JL

    更新日期：1989-08-01 00:00:00

  • Liberating R169 promotes anticoagulant protein C.

    abstract：:In this issue of Blood, Pozzi et al demonstrate that removing an anionic cage promotes exposure of R169 thereby generating a protein C (PC) that is far more readily activated. ...

    journal_title：Blood

    pub_type： 评论,杂志文章

    doi：10.1182/blood-2012-05-427401

    authors： Maurer MC

    更新日期：2012-07-19 00:00:00

  • Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group.

    abstract：:AALL07P2 evaluated whether substitution of Erwinia asparaginase 25000 IU/m(2) for 6 doses given intramuscularly Monday/Wednesday/Friday (M/W/F) to children and young adults with acute lymphoblastic leukemia and clinical allergy to pegaspargase would provide a 48-hour nadir serum asparaginase activity (NSAA) ≥ 0.10 IU/...

    journal_title：Blood

    pub_type： 临床试验,杂志文章

    doi：10.1182/blood-2013-01-480822

    authors： Salzer WL,Asselin B,Supko JG,Devidas M,Kaiser NA,Plourde P,Winick NJ,Reaman GH,Raetz E,Carroll WL,Hunger SP

    更新日期：2013-07-25 00:00:00

  • The T-cell CD2 determinant mediates inhibition of erythropoiesis by the lymphokine cascade.

    abstract：:We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype c...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Burdach S,Shatsky M,Wagenhorst B,Levitt L

    更新日期：1988-08-01 00:00:00

  • Severe factor VII deficiency due to a mutation disrupting a hepatocyte nuclear factor 4 binding site in the factor VII promoter.

    abstract：:Although small deletions, splice site abnormalities, missense, and nonsense mutations have been identified in patients with factor VII deficiency, there have been no reports of mutations in the factor VII promoter. We investigated a girl with factor VII levels that were less than 1% of normal in association with a sev...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Arbini AA,Pollak ES,Bayleran JK,High KA,Bauer KA

    更新日期：1997-01-01 00:00:00

  • Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection.

    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

    authors： Roger T,Lugrin J,Le Roy D,Goy G,Mombelli M,Koessler T,Ding XC,Chanson AL,Reymond MK,Miconnet I,Schrenzel J,François P,Calandra T

    更新日期：2011-01-27 00:00:00

  • Implications of discrepancy in morphologic diagnosis of myelodysplastic syndrome between referral and tertiary care centers.

    abstract：:Patients referred to tertiary care centers occasionally may have their diagnostic procedures repeated and have a final diagnosis that differs from that of the referring center. The aim of this study was to evaluate discordance rates and their clinical implications in the diagnosis of patients with myelodysplastic synd...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2011-03-342642

    authors： Naqvi K,Jabbour E,Bueso-Ramos C,Pierce S,Borthakur G,Estrov Z,Ravandi F,Faderl S,Kantarjian H,Garcia-Manero G

    更新日期：2011-10-27 00:00:00

  • Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1.

    abstract：:Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic prot...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-02-267740

    authors： Meltzer ME,Lisman T,de Groot PG,Meijers JC,le Cessie S,Doggen CJ,Rosendaal FR

    更新日期：2010-07-08 00:00:00

  • Detection of Philadelphia chromosome-positive cells by the polymerase chain reaction following bone marrow transplant for chronic myelogenous leukemia.

    abstract：:Sixteen patients treated by allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr/abl-specific RNA transcripts at various time points after BMT. In reconstitution experiments, one CML cell per million normal mononuclear cells c...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Roth MS,Antin JH,Bingham EL,Ginsburg D

    更新日期：1989-08-01 00:00:00

  • A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.

    abstract：:For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2004-03-1193

    authors： Gunzer M,Weishaupt C,Hillmer A,Basoglu Y,Friedl P,Dittmar KE,Kolanus W,Varga G,Grabbe S

    更新日期：2004-11-01 00:00:00

  • Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

    abstract：:The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Storb R,Prentice RL,Banaji M,Witherspoon RP,Sullivan KM,Stewart P,Sanders JE,Mason M,Doney K,Deeg J,Clift RA,Buckner CD,Appelbaum FR,Thomas ED

    更新日期：1983-04-01 00:00:00

  • Immunophenotypic analysis of B cells in PNH: insights into the generation of circulating naive and memory B cells.

    abstract：:Peripheral blood B cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) comprise variable mixtures of normal B cells produced before the onset of disease and glycosylphosphatidylinositol (GPI)-deficient B cells derived from the PNH hematopoietic stem cell. In a detailed phenotypic analysis of 29 patients w...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Richards SJ,Morgan GJ,Hillmen P

    更新日期：2000-11-15 00:00:00

  • Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers.

    abstract：:Hematide is an investigational pegylated synthetic peptide that stimulates erythropoiesis in animal models and is being developed for the treatment of anemia associated with chronic renal failure and cancer. This study evaluated the safety and pharmacodynamics of single, intravenous doses (0.025, 0.05, and 0.1 mg/kg) ...

    journal_title：Blood

    pub_type： 杂志文章,随机对照试验

    doi：10.1182/blood-2006-04-015818

    authors： Stead RB,Lambert J,Wessels D,Iwashita JS,Leuther KK,Woodburn KW,Schatz PJ,Okamoto DM,Naso R,Duliege AM

    更新日期：2006-09-15 00:00:00

  • Mapping of distinct von Willebrand factor domains interacting with platelet GPIb and GPIIb/IIIa and with collagen using monoclonal antibodies.

    abstract：:We have used monoclonal antibodies (M Abs) and proteolytic fragmentation to localize structurally the functional sites of human von Willebrand factor (vWF) responsible for interaction with membrane glycoproteins GPIb, GPIIb/IIIa, and with collagen. SpII (215 kd) and SpIII (320 kd), the S aureus V-8 protease homodimeri...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Girma JP,Kalafatis M,Piétu G,Lavergne JM,Chopek MW,Edgington TS,Meyer D

    更新日期：1986-05-01 00:00:00

  • High-level expression of Mpl in platelets and megakaryocytes is independent of thrombopoietin.

    abstract：:Thrombopoietin (TPO) is a hematopoietic growth factor that regulates megakaryocytopoiesis and platelet production through binding to its receptor, Mpl, encoded by the c-mpl proto-oncogene. Circulating levels of TPO are regulated by receptor-mediated uptake and degradation. To better understand this mode of TPO regulat...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Cohen-Solal K,Vitrat N,Titeux M,Vainchenker W,Wendling F

    更新日期：1999-05-01 00:00:00

  • Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma.

    abstract：:Interleukin-15 (IL-15) induces proliferation and promotes cell survival of human T and B lymphocytes, natural killer cells, and neutrophils. Here we report the constitutive expression of a functional IL-15 receptor (IL-15R) in 6 of 6 myeloma cell lines and in CD38(high)/CD45(low )plasma cells belonging to 14 of 14 pat...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Tinhofer I,Marschitz I,Henn T,Egle A,Greil R

    更新日期：2000-01-15 00:00:00

  • Repurposing a novel anti-cancer RXR agonist to attenuate acute GVHD and maintain graft-versus-leukemia responses.

    abstract：:The nuclear receptors (NR) retinoid X receptors (RXRs) exert immunomodulatory functions to control inflammation and metabolism via homodimers and heterodimers with several other NRs including retinoic acid receptors. IRX4204 is a novel, highly specific RXR agonist in clinical trials that potently and selectively activ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.2020005628

    authors： Thangavelu G,Wang C,Loschi M,Saha A,Osborn M,Furlan SN,Aoyama K,McDonald-Hyman C,Aguilar EG,Janesick AS,Chandraratna RA,Refaeli Y,Panoskaltsis-Mortari A,MacDonald KP,Hill GR,Zeiser R,Maillard I,Serody J,Murphy WJ,Mu

    更新日期：2020-09-24 00:00:00

  • Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation.

    abstract：:Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host disease and graft failure, negatively influences T-cell IR. We studied the rela...

    journal_title：Blood

    pub_type： 临床试验,杂志文章

    doi：10.1182/blood-2016-06-721936

    authors： Admiraal R,Lindemans CA,van Kesteren C,Bierings MB,Versluijs AB,Nierkens S,Boelens JJ

    更新日期：2016-12-08 00:00:00