Interferon-γ 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, Yoshiyuki Niho

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24 Citations (Scopus)


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-γ (IFN-γ) 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-γ to the culture significantly inhibited their spontaneous apoptosis without inducing cell proliferation or upregulation of Bcl-2. The NK leukemia cells constitutively secreted IFN-γ, and the patients' sera contained a high concentration of IFN-γ, levels that were high enough to prevent NK leukemia cells from apoptosis. Bcl-X(L) was not involved in the IFN-γ-induced NK leukemia cell survival. These data suggest that the acquisition of IFN-γ- mediated autocrine survival signals, other than Bcl-2 or BCL-X(L), might be important for the development of EBV-infected NK leukemia.

Original languageEnglish
Pages (from-to)3494-3504
Number of pages11
Issue number10
Publication statusPublished - May 15 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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