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J. Exp. Med.,
Volume 189, Number 7, April 5, 1999 1063-1071
By
From the * Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute,
the Fas antigen (Apo-1/CD95) is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor receptor superfamily. Adult T cell leukemia (ATL) cells express Fas antigen
and show apoptosis after treatment with an anti-Fas monoclonal antibody. We established the
ATL cell line KOB, which showed resistance to Fas-mediated apoptosis, and found that KOB
expressed two forms of Fas mRNA, the normal form and a truncated form. The truncated transcript lacked 20 base pairs at exon 9, resulting in a frame shift and the generation of a premature stop codon at amino acid 239. The same mutation was detected in primary ascitic cells
and peripheral blood cells. The mutation was not detected in lymph node cells, however, although all of the primary ATL cells were of the same clonal origin. A retroviral-mediated gene
transfer of the truncated Fas to Jurkat cells rendered the cells resistant to Fas-mediated apoptosis, suggesting a dominant negative interference mechanism. These results indicate that an
ATL subclone acquires a Fas mutation in the lymph nodes, enabling the subclone to escape from apoptosis mediated by the Fas/Fas ligand system and proliferate in the body. Mutation of
the Fas gene may be one of the mechanisms underlying the progression of ATL.
Department of Laboratory Medicine, and the § Department of Bacteriology, Nagasaki University
School of Medicine, Nagasaki 852-8102, Japan; and the Department of Laboratory Chemotherapy,
Aichi Cancer Center, Aichi 464-0021, Japan
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