INTERFERON-GAMMA INHIBITS APOPTOSIS INDUCED BY WILD-TYPE P53, CYTOTOXIC ANTICANCER AGENTS AND VIABILITY FACTOR DEPRIVATION IN MYELOID CELLS

Different hematopoietic cytokines including colony-stimulating factors and interleukins can Inhibit apoptotic cell death induced in myeloid cells by the tumor-suppressor gene wildtype 53 and a variety of cytoto xic anti-cancer agents. In this study we identify interferon-gamma as an anti-apoptotic cytokine for myeloid cells in which apoptosis was in duced by wild-type p53, cytotoxic anti-cancer agents or viability fact or deprivation. The inhibition of wild-type p53-mediated apoptosis in myeloid leukemic cells by interferon-gamma was not associated with dow nregulated expression of wild-type p53 or the p53-induced cyclin-depen dent kinase inhibitor gene WAF-1, or with upregulated expression of th e apoptosis-inhibiting gene bcl-2. Interferon-gamma also inhibited ind uction of apoptosis by a p53-independent pathway. Interferon-gamma inh ibited apoptotic cell death caused by withdrawal of viability factors in normal myeloid precursor cells, the interleukin 3-dependent 32D cel l line and differentiating myeloid leukemic cells. Interferon-alpha/be ta did not inhibit apoptotic cell death in any of these systems. The r esults indicate that although interferon-gamma can inhibit cell multip lication and differentiation in myeloid cells, it shares with other he matopoietic cytokines the ability to protect normal and leukemic myelo id cells from induction of apoptosis.