HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma.

Abstract:

:We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.

journal_name

Blood

journal_title

Blood

authors

Zappasodi R,Ruggiero G,Guarnotta C,Tortoreto M,Tringali C,Cavanè A,Cabras AD,Castagnoli L,Venerando B,Zaffaroni N,Gianni AM,De Braud F,Tripodo C,Pupa SM,Di Nicola M

doi

10.1182/blood-2014-07-590034

subject

Has Abstract

pub_date

2015-03-12 00:00:00

pages

1768-71

issue

11

eissn

0006-4971

issn

1528-0020

pii

blood-2014-07-590034

journal_volume

125

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse.

    abstract::Hypercoagulability and thrombotic tendency are frequently induced by a variety of stressors. Clinically, aged subjects and obese patients are more susceptible to thrombotic diseases associated with stress, but the underlying mechanisms are unknown. We investigated the expression of a procoagulant gene, tissue factor (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0945

    authors: Yamamoto K,Shimokawa T,Yi H,Isobe K,Kojima T,Loskutoff DJ,Saito H

    更新日期:2002-12-01 00:00:00

  • Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs.

    abstract::Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene on the X-chromosome that result in skeletal and cardiac muscle damage and premature death. Studies in mice, including the mdx mouse model of DMD, have demonstrated that circulating bone marrow-derived cells can participate in skeletal musc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-06-2247

    authors: Dell'Agnola C,Wang Z,Storb R,Tapscott SJ,Kuhr CS,Hauschka SD,Lee RS,Sale GE,Zellmer E,Gisburne S,Bogan J,Kornegay JN,Cooper BJ,Gooley TA,Little MT

    更新日期:2004-12-15 00:00:00

  • The effect of PGI2 and theophylline on the response of platelets subjected to shear stress.

    abstract::A specially designed rotational viscometer was used to investigate the effects of the antiplatelet agent PGI2 in combination with theophylline on the response of human platelets subjected to shear stress. Samples of citrated platelet-rich plasma (PRP) were exposed to shear stress in the viscometer for a period of 5 mi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hardwick RA,Hellums JD,Peterson DM,Moake JL,Olson JD

    更新日期:1981-10-01 00:00:00

  • Human NK cells at early stages of differentiation produce CXCL8 and express CD161 molecule that functions as an activating receptor.

    abstract::Human natural killer (NK) cell development is a step-by-step process characterized by phenotypically identified stages. CD161 is a marker informative of the NK cell lineage commitment, whereas CD56, CD117, and CD94/NKG2A contribute to define discrete differentiation stages. In cells undergoing in vitro differentiation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-09-379693

    authors: Montaldo E,Vitale C,Cottalasso F,Conte R,Glatzer T,Ambrosini P,Moretta L,Mingari MC

    更新日期:2012-04-26 00:00:00

  • Treatment of hypoplastic anemia in mice with placental transplants.

    abstract::A genetic mutation in mice (W/Wv) causes an autosomal recessive disease characterized by hypoplastic anemia which lasts throughout life. Double-dominant W/Wv anemic mice were sublethally irradiated to facilitate repopulation of marrow with transplanted cells and were injected intravenously with suspensions of 5-10 mil...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dancis J,Jansen V,Brown GF,Gorstein F,Balis ME

    更新日期:1977-10-01 00:00:00

  • Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis.

    abstract::As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor-alpha (TNF-alpha) release and a promoter of interleukin-8 (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Michaels LA,Ohene-Frempong K,Zhao H,Douglas SD

    更新日期:1998-11-01 00:00:00

  • Neutrophil migration is defective during recombinant human granulocyte-macrophage colony-stimulating factor infusion after autologous bone marrow transplantation in humans.

    abstract::We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Peters WP,Stuart A,Affronti ML,Kim CS,Coleman RE

    更新日期:1988-10-01 00:00:00

  • Allogenic fetal liver cells have a distinct competitive engraftment advantage over adult bone marrow cells when infused into fetal as compared with adult severe combined immunodeficient recipients.

    abstract::In utero transplantation (IUT) is becoming a viable option for the treatment of various immune and metabolic disorders diagnosed early in gestation. In this study, donor fetal liver cells had a 10-fold competitive engraftment advantage relative to adult bone marrow in allogeneic fetal severe combined immunodeficient (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.5.1870

    authors: Taylor PA,McElmurry RT,Lees CJ,Harrison DE,Blazar BR

    更新日期:2002-03-01 00:00:00

  • Structural requirements for the activation of human factor VIII by thrombin.

    abstract::The coagulation factors V (FV) and VIII (FVIII) are important at sites of vascular injury for the amplification of the clotting cascade. Natural variants of these factors frequently lead to severe bleeding disorders. To understand the mechanisms of activation of FVIII by thrombin, we used a bank of mutant thrombins to...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0843

    authors: Myles T,Yun TH,Leung LL

    更新日期:2002-10-15 00:00:00

  • Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1.

    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

    authors: Lei W,Liu F,Ness SA

    更新日期:2005-05-15 00:00:00

  • Defective delivery of iron to the developing red cell of the Belgrade laboratory rat.

    abstract::Erythroid cell iron and transferrin uptake and release was studied in the anemia of the Belgrade laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. When reticulocyte-rich red cells were incubated in vitro with doubly (59Fe, 125I) labeled transferrin, b/b cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Edwards JA,Sullivan AL,Hoke JE

    更新日期:1980-04-01 00:00:00

  • Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.

    abstract::The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-07-2283

    authors: Li HY,Appelbaum FR,Willman CL,Zager RA,Banker DE

    更新日期:2003-05-01 00:00:00

  • New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases.

    abstract::A large number of alterations in genes encoding receptor tyrosine kinase (RTK), namely FLT3, c-KIT, platelet-derived growth factor (PDGF) receptors, fibroblast growth factor (FGF) receptors, and the anaplastic large cell lymphoma kinase (ALK), have been found in hematopoietic malignancies. They have drawn much attenti...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2010-04-279752

    authors: Toffalini F,Demoulin JB

    更新日期:2010-10-07 00:00:00

  • Hepatitis C infection among survivors of childhood cancer.

    abstract::Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Strickland DK,Riely CA,Patrick CC,Jones-Wallace D,Boyett JM,Waters B,Fleckenstein JF,Dean PJ,Davila R,Caver TE,Hudson MM

    更新日期:2000-05-15 00:00:00

  • Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump.

    abstract::Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indee...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-04-1398

    authors: Burger H,van Tol H,Boersma AW,Brok M,Wiemer EA,Stoter G,Nooter K

    更新日期:2004-11-01 00:00:00

  • Morphological analysis of microparticle generation in heparin-induced thrombocytopenia.

    abstract::Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To dat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hughes M,Hayward CP,Warkentin TE,Horsewood P,Chorneyko KA,Kelton JG

    更新日期:2000-07-01 00:00:00

  • Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial.

    abstract::We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with avai...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2017-07-795476

    authors: Cottereau AS,Versari A,Loft A,Casasnovas O,Bellei M,Ricci R,Bardet S,Castagnoli A,Brice P,Raemaekers J,Deau B,Fortpied C,Raveloarivahy T,Van Zele E,Chartier L,Vander Borght T,Federico M,Hutchings M,Ricardi U,Andre M

    更新日期:2018-03-29 00:00:00

  • Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells.

    abstract::Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the tr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Skov S,Nielsen M,Bregenholt S,Odum N,Claesson MH

    更新日期:1998-05-15 00:00:00

  • IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor.

    abstract::We recently demonstrated that immunoglobulin E (IgE), in the absence of cross-linking agents, activates signaling pathways in healthy murine bone marrow-derived mast cells (BMMCs) and that this activation enhances BMMC survival, at least in part, via secretion of autocrine-acting cytokines. We report herein that IgE a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-10-3176

    authors: Lam V,Kalesnikoff J,Lee CW,Hernandez-Hansen V,Wilson BS,Oliver JM,Krystal G

    更新日期:2003-08-15 00:00:00

  • Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.

    abstract::Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gribben JG,Neuberg D,Freedman AS,Gimmi CD,Pesek KW,Barber M,Saporito L,Woo SD,Coral F,Spector N

    更新日期:1993-06-15 00:00:00

  • FGFR-1 regulates angiogenesis through cytokines interleukin-4 and pleiotrophin.

    abstract::The role of fibroblast growth factors (FGFs) in blood vessel formation has remained unclear. We used differentiating stem-cell cultures (embryoid bodies) and teratomas to show that FGF receptor-1 (FGFR-1) exerts a negative regulatory effect on endothelial cell function in these models. Embryoid bodies lacking expressi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-01-067314

    authors: Magnusson PU,Dimberg A,Mellberg S,Lukinius A,Claesson-Welsh L

    更新日期:2007-12-15 00:00:00

  • How I treat essential thrombocythemia.

    abstract::In the past 5 years we have witnessed significant advances in both the diagnostic process and optimal therapy for patients with essential thrombocythemia (ET). Insights into the underlying molecular mechanisms have been accompanied by the development of new diagnostic tests and by an improved understanding of the rela...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-08-270033

    authors: Beer PA,Erber WN,Campbell PJ,Green AR

    更新日期:2011-02-03 00:00:00

  • Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2.

    abstract::Chromosomal abnormalities in acute leukemia have led to the discovery of many genes involved in normal hematopoiesis and in malignant transformation. We have identified the fusion partners in an inv(8)(p11q13) from a patient with acute mixed lineage leukemia. We show by fluorescence in situ hybridization (FISH) analys...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Liang J,Prouty L,Williams BJ,Dayton MA,Blanchard KL

    更新日期:1998-09-15 00:00:00

  • A possible autocrine role for interleukin-6 in two lymphoma cell lines.

    abstract::Interleukin-6 (IL-6) is a growth factor with diverse biologic activity. Originally described as a T-cell product that enhances immunoglobulin (Ig) secretion in antigen-stimulated B cells, it also affects the growth of T cells, plasmacytomas, hybridomas, and hematopoietic stem cells. We report the expression and secret...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yee C,Biondi A,Wang XH,Iscove NN,de Sousa J,Aarden LA,Wong GG,Clark SC,Messner HA,Minden MD

    更新日期:1989-08-01 00:00:00

  • Whole-exome sequencing to identify genetic risk variants underlying inhibitor development in severe hemophilia A patients.

    abstract::The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly complication of FVIII replacement therapy that affects up to 30% of previously untreated patients with severe hemophilia A. The development of inhibitors is a multifactorial complication i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-12-685735

    authors: Gorski MM,Blighe K,Lotta LA,Pappalardo E,Garagiola I,Mancini I,Mancuso ME,Fasulo MR,Santagostino E,Peyvandi F

    更新日期:2016-06-09 00:00:00

  • Recombinant prolylcarboxypeptidase activates plasma prekallikrein.

    abstract::The serine protease prolylcarboxypeptidase (PRCP), isolated from human umbilical vein endothelial cells (HUVECs), is a plasma prekallikrein (PK) activator. PRCP cDNA was cloned in pMT/BIP/V5-HIS-C, transfected into Schneider insect (S2) cells, and purified from serum-free media. Full-length recombinant PRCP (rPRCP) ac...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2510

    authors: Shariat-Madar Z,Mahdi F,Schmaier AH

    更新日期:2004-06-15 00:00:00

  • Endothelial Smad4 restrains the transition to hematopoietic progenitors via suppression of ERK activation.

    abstract::In mouse mid-gestational embryos, definitive hematopoietic stem progenitor cells are derived directly from a very small proportion of the arterial endothelium. However, the physiological mechanisms restraining excessive endothelial-hematopoietic transition remain elusive. We show here that genetic deletion of Smad4 fr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-09-526053

    authors: Lan Y,He W,Li Z,Wang Y,Wang J,Gao J,Wang W,Cheng T,Liu B,Yang X

    更新日期:2014-04-03 00:00:00

  • Found: a cellular activating ligand for NKp44.

    abstract::In this issue of Blood, Baychelier et al identify a ligand for a major natural killer (NK) cell receptor that mediates natural cytotoxicity toward tumor cells, thus ending a search that lasted well over a decade. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2013-09-523696

    authors: Rajagopalan S,Long EO

    更新日期:2013-10-24 00:00:00

  • Correlates of spontaneous clearance of hepatitis C virus among people with hemophilia.

    abstract::People with hemophilia were formerly at very high risk of infection with hepatitis C virus (HCV). Approximately 20% of HCV-infected patients spontaneously clear the virus. To identify correlates of spontaneous clearance of HCV, we studied a cohort of HCV-infected hemophilic subjects without human immunodeficiency viru...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2005-07-2781

    authors: Zhang M,Rosenberg PS,Brown DL,Preiss L,Konkle BA,Eyster ME,Goedert JJ,Second Multicenter Hemophilia Cohort Study.

    更新日期:2006-02-01 00:00:00

  • IFN-gamma gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice.

    abstract::Posttransplantation lymphoproliferative disorder (PTLD) is a devastating post-transplantation complication often associated with Epstein-Barr virus (EBV). Although the type and length of immunosuppression are risk factors, a patient's inherent immune capacity also likely contributes to this disorder. This report uses ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2476

    authors: Dierksheide JE,Baiocchi RA,Ferketich AK,Roychowdhury S,Pelletier RP,Eisenbeis CF,Caligiuri MA,VanBuskirk AM

    更新日期:2005-02-15 00:00:00