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Blood. 2008 Dec 1;112(12):4694-8. doi: 10.1182/blood-2008-02-136382. Epub 2008 Sep 12.

Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling.

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Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute Immunology Program, James A Haley Veterans Administration Hospital, University of South Florida, Tampa, FL 33612, USA.


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 as NCI 6823.

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