Blockade of Fas-dependent apoptosis by soluble Fas in LGL leukemia. Journal   Blood. Citation   Blood. 100(4):1449-53 Publication date   2002 Aug 15 Authors   Liu JH Wei S Lamy T Li Y Epling-Burnette PK Djeu JY Loughran TP Investigators   Thomas P. Loughran Grant agencies   National Cancer Institute Grants   NCI CA83947 NCI CA90633 MeSH headings   Antigens, CD95 Apoptosis Leukemia, Lymphoid MeSH qualifiers   genetics physiology pathology Abstract   Altered expression of the Fas-Fas ligand apoptotic pathway leads to lymphoproliferative and autoimmune diseases. In lpr/lpr mice and children with autoimmune lymphoproliferative syndrome, defective apoptosis is due to Fas mutations. Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disorder associated with rheumatoid arthritis. Leukemic LGLs are resistant to Fas-dependent apoptosis despite expressing high levels of Fas. Such resistance can be overcome by activating leukemic LGLs in vitro, suggesting inhibition of Fas signaling in leukemic cells. We report that sera from patients with LGL leukemia contain high levels of soluble Fas. Ten of these 33 patients with LGL leukemia also had rheumatoid arthritis. Cloning and sequencing revealed expression of multiple Fas messenger RNA variants in leukemic LGL. These Fas variants, including 3 newly described here, encode soluble Fas molecules. Supernatants from cells transfected with these Fas variants blocked Fas-dependent apoptosis of leukemic LGLs. These results suggest that blockade of Fas-signaling by soluble Fas may be a mechanism leading to apoptosis resistance in leukemic LGLs. Medline ID   22144024