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Titolo:
Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors
Autore:
Emanuel, PD; Snyder, RC; Wiley, T; Gopurala, B; Castleberry, RP;
Indirizzi:
Univ Alabama, Ctr Comprehens Canc, Dept Med, Div Hematol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 iv Hematol, Birmingham, AL 35294 USA Univ Alabama, Ctr Comprehens Canc, Dept Med, Div Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Div Oncol, Birmingham, AL 35294 USA Univ Alabama, Ctr Comprehens Canc, Dept Pediat, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Pediat, Birmingham, AL 35294 USA
Titolo Testata:
BLOOD
fascicolo: 2, volume: 95, anno: 2000,
pagine: 639 - 645
SICI:
0006-4971(20000115)95:2<639:IOJMLC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; FARNESYL-PROTEIN TRANSFERASE; MALIGNANT MYELOID DISORDERS; INTENSIVE COMBINATION CHEMOTHERAPY; ALLOGENEIC MARROW TRANSPLANTATION; GTP-BINDING PROTEINS; N-RAS; MYELODYSPLASTIC SYNDROMES; TRANSGENIC MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
85
Recensione:
Indirizzi per estratti:
Indirizzo: Emanuel, PD Univ Alabama, Walace Tumor Inst, Div Hematol Oncol, Suite 520,Birmingham,AL 35294 USA Univ Alabama Suite 520 Birmingham AL USA 35294 am,AL 35294 USA
Citazione:
P.D. Emanuel et al., "Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors", BLOOD, 95(2), 2000, pp. 639-645

Abstract

Juvenile myelomonocytic leukemia (JMML) is an early childhood disease for which there is no effective therapy. Therapy with 13-cis retinoic acid or low-dose chemotherapy can induce some responses, but neither mode is curative, Stem cell transplantation can produce lasting remissions but is hamperedby high rates of relapse. The pathogenesis of JMML involves deregulated cytokine signal transduction through the Ras signaling pathway, with resultant selective hypersensitivity of JMML cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). A JMML mouse model, achieved through homozygous deletion of the neurofibromatosis gene, confirmed the involvement of deregulated Ras in JMML pathogenesis, With this pathogenetic knowledge, mechanism-based treatments are now being developed and tested, Ras is critically dependent on a prenylation reaction for its signal transduction abilities. Farnesyltransferase inhibitors are compounds that were developed specifically to block the prenylation of Pas. Two of these compounds, L-739,749 and L-744,832, were tested for their ability to inhibit spontaneous JMML granulocyte-macrophage colony growth, Within a dose range of 1 to 10 mu mol/L, each compound demonstrated dose-dependent inhibition of JMML colony growth. Anage-matched patient with a different disease and GM-CSF-stimulated normal adult marrow cells also demonstrated dose-dependent inhibitory effects on colony growth, but they were far less sensitive to these compounds than JMMLhematopoietic progenitors. Even if the addition of L-739,749 were delayed for 5 days, significant inhibitory effects would still show in JMML cultures. These results demonstrate that a putative Ras-blocking compound can havesignificant growth inhibitory effects in vitro, perhaps indicating a potential treatment for JMML.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:34:49