Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling.
Blood
; 112(12): 4694-8, 2008 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-18791165
ABSTRACT
Large granular lymphocyte (LGL) leukemia is commonly associated with poor hematopoiesis. The first case of pulmonary artery hypertension (PAH) was observed in a 57-year-old woman with natural killer (NK)-LGL leukemia and transfusion-dependent anemia. Using a genetic approach, we demonstrated that killing of pulmonary endothelial cells by patient NK cells was mediated by dysregulated balance in activating and inhibitory NK-receptor signaling. Elevated pulmonary artery pressure and erythroid differentiation improved after disrupting the NK-receptor signaling pathway with 4 courses of a farnesyltransferase inhibitor, tipifarnib. Coincidental association between PAH and LGL leukemia suggest a causal relationship between the expanded lymphocyte population and these clinical manifestations. This trial is registered at www.ClinicalTrials.gov as NCI 6823.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Farnesiltranstransferase
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Leucemia Linfocítica Granular Grande
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Receptores de Células Matadoras Naturais
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Antineoplásicos
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article