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.
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5 April 1999
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April 05 1999
Fas Gene Mutation in the Progression of Adult T Cell Leukemia
Takahiro Maeda,
Takahiro Maeda
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Yasuaki Yamada,
Yasuaki Yamada
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Ryozou Moriuchi,
Ryozou Moriuchi
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Kazuyuki Sugahara,
Kazuyuki Sugahara
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Kazuto Tsuruda,
Kazuto Tsuruda
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Tatsurou Joh,
Tatsurou Joh
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Sunao Atogami,
Sunao Atogami
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Kunihiro Tsukasaki,
Kunihiro Tsukasaki
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Masao Tomonaga,
Masao Tomonaga
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Shimeru Kamihira
Shimeru Kamihira
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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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Takahiro Maeda
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Yasuaki Yamada
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Ryozou Moriuchi
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Kazuyuki Sugahara
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Kazuto Tsuruda
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Tatsurou Joh
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Sunao Atogami
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Kunihiro Tsukasaki
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Masao Tomonaga
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Shimeru Kamihira
From the *Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, the ‡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
Address correspondence to Takahiro Maeda, Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, 1-7-1 Sakamoto-machi, Nagasaki 852-8102, Japan. Phone: 81-95-849-7380; Fax: 81-95-849-7538; E-mail: [email protected]
Received:
December 01 1998
Revision Received:
January 25 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (7): 1063–1071.
Article history
Received:
December 01 1998
Revision Received:
January 25 1999
Citation
Takahiro Maeda, Yasuaki Yamada, Ryozou Moriuchi, Kazuyuki Sugahara, Kazuto Tsuruda, Tatsurou Joh, Sunao Atogami, Kunihiro Tsukasaki, Masao Tomonaga, Shimeru Kamihira; Fas Gene Mutation in the Progression of Adult T Cell Leukemia . J Exp Med 5 April 1999; 189 (7): 1063–1071. doi: https://doi.org/10.1084/jem.189.7.1063
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