In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells.

Abstract:

:Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltransferase inhibitor (FTI) L-744,832 in an in vivo murine model of myeloid leukemia that is associated with inactivation of the Nf1 tumor suppressor gene. Nf1 encodes a GTPase activating protein for Ras, and Nf1-deficient (Nf1-/-) hematopoietic cells show hyperactive Ras signaling through the mitogen-activated protein (MAP) kinase pathway. L-744,832 inhibited H-Ras prenylation in cell lines and in primary hematopoietic cells and abrogated the in vitro growth of myeloid progenitor colonies in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). This FTI also partially blocked GM-CSF-induced MAP kinase activation, but did not reduce constitutively elevated levels of MAP kinase activity in primary Nf1-/- cells. Injection of a single dose of 40 or 80 mg/kg of L-744, 832 increased the amount of unprocessed H-Ras in bone marrow cells, but had no detectable effect on N-Ras. Adoptive transfer of Nf1-/- hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment. We speculate that the lack of efficacy in this model is due to the resistance of N-Ras and K-Ras processing to inhibition by this FTI.

journal_name

Blood

journal_title

Blood

authors

Mahgoub N,Taylor BR,Gratiot M,Kohl NE,Gibbs JB,Jacks T,Shannon KM

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

2469-76

issue

7

eissn

0006-4971

issn

1528-0020

journal_volume

94

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.

    abstract::We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixtee...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:

    authors: Haddad E,Landais P,Friedrich W,Gerritsen B,Cavazzana-Calvo M,Morgan G,Bertrand Y,Fasth A,Porta F,Cant A,Espanol T,Müller S,Veys P,Vossen J,Fischer A

    更新日期:1998-05-15 00:00:00

  • JAK2 inhibitors for myeloproliferative neoplasms: what is next?

    abstract::Since its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant or intolerant polycythemia vera (PV) is steadily increasing. Several other JAK2 inhibitors have entered clinical te...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2017-04-742288

    authors: Bose P,Verstovsek S

    更新日期:2017-07-13 00:00:00

  • Activation peptides prolong the murine plasma half-life of human factor VII.

    abstract::Coagulation factors VII (FVII), IX (FIX), X (FX), and protein C share the same domain organization but display very different plasma half-lives. It is plausible that the half-life is influenced by the activation peptide, differing in length and glycosylation and missing in FVII. To test this hypothesis, the influence ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-06-290098

    authors: Johansson L,Karpf DM,Hansen L,Pelzer H,Persson E

    更新日期:2011-03-24 00:00:00

  • The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.

    abstract::The role of hematopoietic growth factors in lineage commitment and differentiation is unclear. We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin recept...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Harris KW,Hu XJ,Schultz S,Arcasoy MO,Forget BG,Clare N

    更新日期:1998-08-15 00:00:00

  • Hematopoietic precursors resistant to treatment with 4-hydroperoxycyclophosphamide: requirement for an interaction with marrow stroma in addition to hematopoietic growth factors for maximal generation of colony-forming activity.

    abstract::We tested the ability of CD34+lin- precursor cells isolated from marrow after treatment with 4-hydroperoxycyclophosphamide (4HC) to generate colony-forming cells (CFC). In liquid cultures, recombinant human stem cell factor (SCF), in combination with interleukin-1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stim...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rowley SD,Brashem-Stein C,Andrews R,Bernstein ID

    更新日期:1993-07-01 00:00:00

  • Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience.

    abstract::The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improv...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-04-423178

    authors: D'Souza A,Lacy M,Gertz M,Kumar S,Buadi F,Hayman S,Dingli D,Zeldenrust S,Kyle R,Ansell S,Inwards D,Johnston P,Micallef I,Porrata L,Litzow M,Gastineau D,Hogan W,Dispenzieri A

    更新日期:2012-07-05 00:00:00

  • Alloantigen presentation and graft-versus-host disease: fuel for the fire.

    abstract::Allogeneic stem cell transplantation (SCT) is a unique procedure, primarily in patients with hematopoietic malignancies, involving chemoradiotherapy followed by the introduction of donor hematopoietic and immune cells into an inflamed and lymphopenic environment. Interruption of the process by which recipient alloanti...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-02-697250

    authors: Koyama M,Hill GR

    更新日期:2016-06-16 00:00:00

  • Erythrocyte deformation in shear flow: influences of internal viscosity, membrane stiffness, and hematocrit.

    abstract::The effect of shear force (depending on shear rate and viscosity of extracellular medium) and hematocrit of RBC suspension on RBC deformation was studied quantitatively using a cone-plate rheoscope with various kinds of cells, ie, partially hemolyzed (PH) cells, density-fractionated intact cells, and diamide-treated c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kon K,Maeda N,Shiga T

    更新日期:1987-03-01 00:00:00

  • Exposure of R169 controls protein C activation and autoactivation.

    abstract::Protein C is activated by thrombin with a value of k(cat)/K(m) = 0.11mM(-1)s(-1) that increases 1700-fold in the presence of the cofactor thrombomodulin. The molecular origin of this effect triggering an important feedback loop in the coagulation cascade remains elusive. Acidic residues in the activation domain of pro...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-03-415323

    authors: Pozzi N,Barranco-Medina S,Chen Z,Di Cera E

    更新日期:2012-07-19 00:00:00

  • Nuclear factor-kappaB activation by the photochemotherapeutic agent verteporfin.

    abstract::The nuclear factor-kappa B (NF-kappaB) gene transactivator serves in the formation of immune, inflammatory, and stress responses. In quiescent cells, NF-kappaB principally resides within the cytoplasm in association with inhibitory kappa (IkappaB) proteins. The status of IkappaB and NF-kappaB proteins was evaluated fo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Granville DJ,Carthy CM,Jiang H,Levy JG,McManus BM,Matroule JY,Piette J,Hunt DW

    更新日期:2000-01-01 00:00:00

  • Long noncoding RNAs in biology and hematopoiesis.

    abstract::Genome and transcriptome sequencing have revealed a rich assortment of noncoding RNAs in eukaryote cells, including long noncoding RNAs (lncRNAs), which regulate gene expression independent of protein coding potential. LncRNAs modulate protein coding gene expression in many cell types by regulating multiple processes,...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2013-03-456111

    authors: Paralkar VR,Weiss MJ

    更新日期:2013-06-13 00:00:00

  • Altered factor VII activity in hemophilia.

    abstract::Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978-988, 1978); and a coupled amidolytic assay. By the FVIIc-B ass...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miller BC,Hultin MB,Jesty J

    更新日期:1985-04-01 00:00:00

  • Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses.

    abstract::Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8(+) and CD4(+) T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor,...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-03-148072

    authors: Gurer C,Strowig T,Brilot F,Pack M,Trumpfheller C,Arrey F,Park CG,Steinman RM,Münz C

    更新日期:2008-08-15 00:00:00

  • Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors.

    abstract::Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in pa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jabado N,de Graeff-Meeder ER,Cavazzana-Calvo M,Haddad E,Le Deist F,Benkerrou M,Dufourcq R,Caillat S,Blanche S,Fischer A

    更新日期:1997-12-15 00:00:00

  • A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo.

    abstract::We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression casse...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.11.3923

    authors: Ehrhardt A,Kay MA

    更新日期:2002-06-01 00:00:00

  • Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.

    abstract::Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stiff PJ,Schulz WC,Bishop M,Marks L

    更新日期:1991-01-15 00:00:00

  • Dominant-negative C/ebpα and polycomb group protein Bmi1 extend short-lived hematopoietic stem/progenitor cell life span and induce lethal dyserythropoiesis.

    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

    authors: Zhou T,Wang L,Zhu KY,Dong M,Xu PF,Chen Y,Chen SJ,Chen Z,Deng M,Liu TX

    更新日期:2011-10-06 00:00:00

  • Retinoic acid inhibits CD40 + interleukin-4-mediated IgE production in vitro.

    abstract::To elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 (1 microgram/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells (PBMC) and B cells in healt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Worm M,Krah JM,Manz RA,Henz BM

    更新日期:1998-09-01 00:00:00

  • Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation.

    abstract::To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sokal JE,Baccarani M,Tura S,Fiacchini M,Cervantes F,Rozman C,Gomez GA,Galton DA,Canellos GP,Braun TJ

    更新日期:1985-12-01 00:00:00

  • Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins.

    abstract::Investigators in the United Kingdom have shown that hereditary amyloidosis can be misdiagnosed as Ig light-chain (AL) amyloidosis because family history is an ineffective screen, and tissue staining used to type amyloid is unreliable. Misdiagnosis of AL can lead to inappropriate use of chemotherapy and failure to diag...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4148

    authors: Comenzo RL,Zhou P,Fleisher M,Clark B,Teruya-Feldstein J

    更新日期:2006-05-01 00:00:00

  • Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis.

    abstract::Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lac...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McCarty KS Jr,Wortman J,Daly J,Rundles RW,Hanker JS

    更新日期:1980-07-01 00:00:00

  • Interaction of Sp1 with the human gamma globin promoter: binding and transactivation of normal and mutant promoters.

    abstract::We have analyzed the binding of Sp1, a ubiquitously expressed transactivator, to the promoter region of the gamma genes. Low-affinity Sp1 sites were found at -50 and -200. A high-affinity site was detected at -140, over the CACCC sequence. To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gumucio DL,Rood KL,Blanchard-McQuate KL,Gray TA,Saulino A,Collins FS

    更新日期:1991-10-01 00:00:00

  • Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels.

    abstract::The extended use of brentuximab-vedotin was reported for CD30(+) nonanaplastic peripheral T-cell lymphomas (PTCLs) with promising efficacy. CD30 status assessment is thus a critical factor for therapeutic decision, but the reliability of immunohistochemistry (IHC) in evaluating its expression remains to be defined. Th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-07-584953

    authors: Bossard C,Dobay MP,Parrens M,Lamant L,Missiaglia E,Haioun C,Martin A,Fabiani B,Delarue R,Tournilhac O,Delorenzi M,Gaulard P,de Leval L

    更新日期:2014-11-06 00:00:00

  • Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men.

    abstract::We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Pollmächer T,Korth C,Mullington J,Schreiber W,Sauer J,Vedder H,Galanos C,Holsboer F

    更新日期:1996-02-01 00:00:00

  • Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID.

    abstract::We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (3...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3443

    authors: Dijkman R,Tensen CP,Buettner M,Niedobitek G,Willemze R,Vermeer MH

    更新日期:2006-06-15 00:00:00

  • Genistein reduces tumor necrosis factor alpha-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.

    abstract::The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PA...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: van Hinsbergh VW,Vermeer M,Koolwijk P,Grimbergen J,Kooistra T

    更新日期:1994-11-01 00:00:00

  • The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2.

    abstract::The CXC-chemokines interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2), and melanoma growth-stimulatory activity (MGSA) are chemoattractants with high selectivity for neutrophils. Although IL-8 has been shown to act as an extremely potent mediator, reports on NAP-2 and MGSA are still contradictory. Here we s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ludwig A,Petersen F,Zahn S,Götze O,Schröder JM,Flad HD,Brandt E

    更新日期:1997-12-01 00:00:00

  • Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma.

    abstract::Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-02-0475

    authors: Kleinhans M,Tun-Kyi A,Gilliet M,Kadin ME,Dummer R,Burg G,Nestle FO

    更新日期:2003-02-15 00:00:00

  • How I treat infant leukemia.

    abstract::Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its fascinating biology. Increasingly, these biological insights are pointing the way toward novel therapeutic approaches. Using represent...

    journal_title:Blood

    pub_type: 杂志文章,随机对照试验

    doi:10.1182/blood-2018-04-785980

    authors: Brown P,Pieters R,Biondi A

    更新日期:2019-01-17 00:00:00

  • Bioengineering of coagulation factor VIII for improved secretion.

    abstract::Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitud...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-10-3591

    authors: Miao HZ,Sirachainan N,Palmer L,Kucab P,Cunningham MA,Kaufman RJ,Pipe SW

    更新日期:2004-05-01 00:00:00