FTY720 demonstrates promising preclinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphoma.

Abstract:

:FTY720 is an immunosuppressant developed to prevent organ transplant rejection. Recent studies indicate an additional role for FTY720 in inducing cell apoptosis. We demonstrate here that FTY720 mediates toxic effects in cell lines representing different B-cell malignancies and primary B cells from patients with chronic lymphocytic leukemia (CLL). In contrast to previous reports in T-cell lines, FTY720-induced toxicity in the Raji cell line and primary CLL B cells is independent of activation of caspases or poly(ADP-ribose) polymerase processing. Further, pancaspase inhibitor Z-VAD-fmk failed to rescue these cells from apoptosis mediated by FTY720. FTY720 induced down-regulation of Mcl-1 but not Bcl-2 in CLL B cells. Overexpression of Bcl-2 failed to protect transformed B cells from FTY720-induced apoptosis, suggesting a Bcl-2-independent mechanism. Interestingly, FTY720 induced protein phosphatase 2a (PP2a) activation and downstream dephosphorylation of ERK1/2, whereas okadaic acid at concentrations that inhibited the FTY720-induced PP2a activation also resulted in inhibition of FTY720-mediated apoptosis and restoration of baseline ERK1/2 phosphorylation in primary CLL cells, indicating a role for PP2a activation in FTY720-induced cytotoxicity. Further, FTY720 treatment resulted in significant prolonged survival in a xenograft severe combined immunodeficiency (SCID) mouse model of disseminated B-cell lymphoma/leukemia. These results provide the first evidence for the potential use of FTY720 as a therapeutic agent in a variety of B-cell malignancies, including CLL.

journal_name

Blood

journal_title

Blood

authors

Liu Q,Zhao X,Frissora F,Ma Y,Santhanam R,Jarjoura D,Lehman A,Perrotti D,Chen CS,Dalton JT,Muthusamy N,Byrd JC

doi

10.1182/blood-2006-10-053884

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

275-84

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2006-10-053884

journal_volume

111

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Loss of DGKε induces endothelial cell activation and death independently of complement activation.

    abstract::Atypical hemolytic uremic syndrome (aHUS) is classically described to result from a dysregulation of the complement alternative pathway, leading to glomerular endothelial cell (EC) damage and thrombosis. However, recent findings in families with aHUS of mutations in the DGKE gene, which is not an integral component of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-06-579953

    authors: Bruneau S,Néel M,Roumenina LT,Frimat M,Laurent L,Frémeaux-Bacchi V,Fakhouri F

    更新日期:2015-02-05 00:00:00

  • Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues.

    abstract::To increase transgenic production of granulocyte-macrophage colony-stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rajagopalan LE,Burkholder JK,Turner J,Culp J,Yang NS,Malter JS

    更新日期:1995-10-01 00:00:00

  • Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis.

    abstract::Lipoprotein (a) [Lp(a)] has been associated with both anti-fibrinolytic and atherogenic effects. However, no direct link currently exists between this atherogenic lipoprotein and intravascular coagulation. The current study examined the binding and functional effects of Lp(a), its lipoprotein constituents, apoliprotei...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.10.2980

    authors: Caplice NM,Panetta C,Peterson TE,Kleppe LS,Mueske CS,Kostner GM,Broze GJ Jr,Simari RD

    更新日期:2001-11-15 00:00:00

  • Identification of the platelet-specific alloantigen, Naka, on platelet membrane glycoprotein IV.

    abstract::We describe the membrane localization of a new platelet-specific alloantigen, designated Naka, that is involved in refractoriness to HLA-matched platelet transfusions. By indirect immunoprecipitation, anti-Naka antibody precipitated a single, radiolabeled platelet membrane protein with a molecular weight (mol wt) of 9...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tomiyama Y,Take H,Ikeda H,Mitani T,Furubayashi T,Mizutani H,Yamamoto N,Tandon NN,Sekiguchi S,Jamieson GA

    更新日期:1990-02-01 00:00:00

  • alpha-Actinin and vinculin in normal and thrombasthenic platelets.

    abstract::Recently, the contractile protein alpha-actinin was identified in normal human platelets by its antigenic cross-reaction with a monospecific antibody to purified muscle alpha-actinin. In this study, we extend that preliminary identification of platelet alpha-actinin. Amino acid analysis, one-dimensional peptide maps, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Langer BG,Gonnella PA,Nachmias VT

    更新日期:1984-03-01 00:00:00

  • Perioperative management of patients on chronic antithrombotic therapy.

    abstract::Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the ris...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2012-05-423228

    authors: Ortel TL

    更新日期:2012-12-06 00:00:00

  • Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.

    abstract::Ravulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete, and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority of ravulizumab to eculizumab in complement inhibitor-naive adults with paroxysmal nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogen...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2018-09-876136

    authors: Lee JW,Sicre de Fontbrune F,Wong Lee Lee L,Pessoa V,Gualandro S,Füreder W,Ptushkin V,Rottinghaus ST,Volles L,Shafner L,Aguzzi R,Pradhan R,Schrezenmeier H,Hill A

    更新日期:2019-02-07 00:00:00

  • Transcription of the activating receptor NKG2D in natural killer cells is regulated by STAT3 tyrosine phosphorylation.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is considered a negative regulator of inflammation, as inhibition of STAT3 signaling enhances antitumor immunity. However, STAT3 activation is a key oncogenic pathway in natural killer (NK)-lineage large granular lymphomas, and we recently reported enhanced pr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-05-499707

    authors: Zhu S,Phatarpekar PV,Denman CJ,Senyukov VV,Somanchi SS,Nguyen-Jackson HT,Mace EM,Freeman AF,Watowich SS,Orange JS,Holland SM,Lee DA

    更新日期:2014-07-17 00:00:00

  • Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia.

    abstract::The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both col...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelleher C,Miyauchi J,Wong G,Clark S,Minden MD,McCulloch EA

    更新日期:1987-05-01 00:00:00

  • Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation.

    abstract::Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-03-0935

    authors: Chou J,Mackman N,Merrill-Skoloff G,Pedersen B,Furie BC,Furie B

    更新日期:2004-11-15 00:00:00

  • Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up-regulate it rapidly to the cell surface upon activation.

    abstract::Activation and subsequent differentiation of naive CD8+ T cells lead to the development of memory subsets with distinct homing and effector capacities. On nonlymphoid homing subsets, expression of "inflammatory" chemokine receptors (such as CXCR3, CCR5, CX3CR1, and CXCR1) is believed to promote migration into sites of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-04-1366

    authors: Gasser O,Missiou A,Eken C,Hess C

    更新日期:2005-12-01 00:00:00

  • Am"B"valent: anti-CD20 antibodies unravel the dual role of B cells in immunopathogenesis.

    abstract::Accumulating evidence has designated B cells as central players in the pathogenesis of immune diseases. In the late 1990s, anti-CD20 monoclonal antibodies were developed for the treatment of B-cell non-Hodgkin lymphomas, offering the opportunity to efficiently deplete the B-cell compartment for therapeutic immunointer...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2010-01-266668

    authors: Thaunat O,Morelon E,Defrance T

    更新日期:2010-07-29 00:00:00

  • Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice.

    abstract::Caloric restriction (CR) is proposed to decrease tumorigenesis through a variety of mechanisms including effects on glycolysis. However, the understanding of how CR affects the response to cancer therapy is still rudimentary. Here, using the Eµ-Myc transgenic mouse model of B-cell lymphoma, we report that by reducing ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-01-478651

    authors: Meynet O,Zunino B,Happo L,Pradelli LA,Chiche J,Jacquin MA,Mondragón L,Tanti JF,Taillan B,Garnier G,Reverso-Meinietti J,Mounier N,Michiels JF,Michalak EM,Carles M,Scott CL,Ricci JE

    更新日期:2013-10-03 00:00:00

  • T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets.

    abstract::Monocytes and T helper (T(H)) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that T(H) cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-03-341065

    authors: Alonso MN,Wong MT,Zhang AL,Winer D,Suhoski MM,Tolentino LL,Gaitan J,Davidson MG,Kung TH,Galel DM,Nadeau KC,Kim J,Utz PJ,Söderström K,Engleman EG

    更新日期:2011-09-22 00:00:00

  • Ethical considerations in genomic testing for hematologic disorders.

    abstract::As our technological capacities improve, genomic testing is increasingly integrating into patient care. The field of clinical hematology is no exception. Genomic testing carries great promise, but several ethical issues must be considered whenever such testing is performed. This review addresses these ethical consider...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2017-01-734558

    authors: Marron JM,Joffe S

    更新日期:2017-07-27 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

  • Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis.

    abstract::Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice defi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.1.192

    authors: Street SE,Cretney E,Smyth MJ

    更新日期:2001-01-01 00:00:00

  • Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model.

    abstract::Growing evidence indicates antibody-dependent cellular cytotoxicity (ADCC) contributes to the clinical response to monoclonal antibody (mAb) therapy of lymphoma. Recent in vitro analysis suggests C3b can inhibit mAb-induced natural killer (NK)-cell activation and ADCC. Further studies were conducted to assess the effe...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-01-200469

    authors: Wang SY,Veeramani S,Racila E,Cagley J,Fritzinger DC,Vogel CW,St John W,Weiner GJ

    更新日期:2009-12-17 00:00:00

  • Host natural killer T cells induce an interleukin-4-dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease.

    abstract::Although CD4(+)CD25(+) T cells (T regulatory cells [Tregs]) and natural killer T cells (NKT cells) each protect against graft-versus-host disease (GVHD), interactions between these 2 regulatory cell populations after allogeneic bone marrow transplantation (BMT) have not been studied. We show that host NKT cells can in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-06-165506

    authors: Pillai AB,George TI,Dutt S,Strober S

    更新日期:2009-04-30 00:00:00

  • Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis.

    abstract::The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characteriz...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-06-723742

    authors: Iwamura C,Bouladoux N,Belkaid Y,Sher A,Jankovic D

    更新日期:2017-01-12 00:00:00

  • Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy.

    abstract::Anemia is a common clinical problem, and there is much interest in its role in promoting left ventricular hypertrophy through increasing cardiac workload. Normally, red blood cell production is adjusted through the regulation of erythropoietin (Epo) production by the kidney. One important cause of anemia is relative d...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-02-0605

    authors: Binley K,Askham Z,Iqball S,Spearman H,Martin L,de Alwis M,Thrasher AJ,Ali RR,Maxwell PH,Kingsman S,Naylor S

    更新日期:2002-10-01 00:00:00

  • Association of an interleukin abnormality with the T cell defect in Hodgkin's disease.

    abstract::The cellular immune defect in untreated Hodgkin's disease (HD) has long been recognized. This defect appears to be responsible for at least some of the morbidity and ultimately the mortality associated with the disease. In recent years, many studies have shown that the T cell component of the immune response is the ap...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ford RJ,Tsao J,Kouttab NM,Sahasrabuddhe CG,Mehta SR

    更新日期:1984-08-01 00:00:00

  • Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development.

    abstract::The expression of Pax5 commits common lymphoid progenitor cells to B-lymphoid lineage differentiation. Little is known of possible variations in the levels of Pax5 expression and their influences on hematopoietic development. We have developed a retroviral transduction system that allows for the study of possible inte...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-03-414821

    authors: Simmons S,Knoll M,Drewell C,Wolf I,Mollenkopf HJ,Bouquet C,Melchers F

    更新日期:2012-11-01 00:00:00

  • Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry.

    abstract::Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Weil GJ,Chused TM

    更新日期:1981-06-01 00:00:00

  • Clonal competition with alternating dominance in multiple myeloma.

    abstract::Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few ch...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-01-405985

    authors: Keats JJ,Chesi M,Egan JB,Garbitt VM,Palmer SE,Braggio E,Van Wier S,Blackburn PR,Baker AS,Dispenzieri A,Kumar S,Rajkumar SV,Carpten JD,Barrett M,Fonseca R,Stewart AK,Bergsagel PL

    更新日期:2012-08-02 00:00:00

  • Epidermis instructs skin homing receptor expression in human T cells.

    abstract::The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. Although the mechanisms controlling memory T-cell migration to peripheral tissues are poorly understood, the current paradigm includes the localized secretion of "imprinting" signal...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-05-433037

    authors: McCully ML,Ladell K,Hakobyan S,Mansel RE,Price DA,Moser B

    更新日期:2012-11-29 00:00:00

  • RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

    abstract::The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a hi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-07-099366

    authors: Schmitt M,Schmitt A,Rojewski MT,Chen J,Giannopoulos K,Fei F,Yu Y,Götz M,Heyduk M,Ritter G,Speiser DE,Gnjatic S,Guillaume P,Ringhoffer M,Schlenk RF,Liebisch P,Bunjes D,Shiku H,Dohner H,Greiner J

    更新日期:2008-02-01 00:00:00

  • SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells.

    abstract::Fanconi anemia (FA) is a hereditary disorder caused by mutations in any 1 of 22 FA genes. The disease is characterized by hypersensitivity to interstrand crosslink (ICL) inducers such as mitomycin C (MMC). In addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication fork...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019003782

    authors: Okamoto Y,Abe M,Mu A,Tempaku Y,Rogers CB,Mochizuki AL,Katsuki Y,Kanemaki MT,Takaori-Kondo A,Sobeck AT,Bielinsky AK,Takata M

    更新日期:2020-07-31 00:00:00

  • Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with Pbx and a novel function of the Meis1 C-terminus.

    abstract::Meis1 is a homeodomain transcription factor coexpressed with Hoxa9 in most human acute myeloid leukemias (AMLs). In mouse models of leukemia produced by Hoxa9, Meis1 accelerates leukemogenesis. Because Hoxa9 immortalizes myeloid progenitors in the absence of Meis1 expression, the contribution of Meis1 toward leukemia ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-12-4664

    authors: Wang GG,Pasillas MP,Kamps MP

    更新日期:2005-07-01 00:00:00

  • Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McNiece IK,Robinson BE,Quesenberry PJ

    更新日期:1988-07-01 00:00:00