Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3494-3504
Interferon-
Prevents Apoptosis in Epstein-Barr Virus-Infected
Natural Killer Cell Leukemia in an Autocrine Fashion
Shin-ichi Mizuno,
Koichi Akashi,
Koichi Ohshima,
Hiromi Iwasaki,
Toshihiro Miyamoto,
Naoyuki Uchida,
Tsunefumi Shibuya,
Mine Harada,
Masahiro Kikuchi, and
Yoshiyuki Niho
From the First Department of Internal Medicine, Faculty of Medicine,
Kyushu University, Fukuoka, Japan; the Department of Pathology,
Stanford Univesity School of Medicine, Stanford, CA; and the First
Department of Pathology, Fukuoka University, Fukuoka, Japan.
The significant function of cytokines includes maintenance of cell
survival as well as induction of cell differentiation and/or proliferation. We demonstrate here that interferon-
(IFN-) plays a role for progression of Epstein-Barr virus (EBV)-infected natural killer cell leukemia (NK leukemia) through maintaining cell survival. NK leukemia cells obtained from 7 patients had clonal episomal forms of
EBV, indicating that the leukemic cells were of clonal origin. Although
normal NK cells constitutively expressed Bcl-2, the EBV-infected NK
leukemia cells lacked endogenous Bcl-2 expression and were
hypersensitive to apoptosis in vitro. The addition of IFN- to the
culture significantly inhibited their spontaneous apoptosis without
inducing cell proliferation or upregulation of Bcl-2. The NK leukemia
cells constitutively secreted IFN-, and the patients' sera
contained a high concentration of IFN-, levels that were high enough
to prevent NK leukemia cells from apoptosis. Bcl-XL was not
involved in the IFN--induced NK leukemia cell survival. These data
suggest that the acquisition of IFN--mediated autocrine survival
signals, other than Bcl-2 or BCL-XL, might be important for
the development of EBV-infected NK leukemia.
