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Medline ® Abstract for Reference 40

of 'Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia'

Constitutive expression of Fas ligand in large granular lymphocyte leukaemia.
Perzova R, Loughran TP Jr
Br J Haematol. 1997;97(1):123.
The T-cell type of large granular lymphocyte (LGL) leukaemia is a lymphoproliferative disorder characterized by clonal proliferation of CD3+ LGL, which is often associated with autoimmune disorders. Phenotypic and functional data suggest that leukaemic CD3+ LGL represent activated cytotoxic T lymphocytes (CTL). One mechanism whereby CTL mediate target cell killing is through the Fas/Fas ligand apoptotic pathway. Fas ligand is expressed by CTL only after activation. In this study we examined seven patients with LGL leukaemia for expression of Fas ligand gene transcripts using reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. We found constitutive expression of Fas ligand gene transcripts in each of the seven patients. Similar up-regulation of Fas ligand gene expression has been observed in mice with autoimmune lymphoproliferative syndromes caused by Fas mutations. However, sequence analyses of the death domain of the Fas gene in LGL leukaemia patients revealed no evidence for mutations. Our findings provide further support for the hypothesis that leukaemic LGL are CTL activated by chronic antigenic stimulation. Constitutive expression of Fas ligand may contribute to the pathogenesis of the neutropenia observed in LGL leukaemia.
Veteran's Administration Hospital and Department of Medicine, State University of New York, Syracuse, U.S.A.