FAS APO-1 (CD95)-MEDIATED APOPTOSIS IS ACTIVATED BY INTERFERON-GAMMA AND INTERFERON-ALPHA IN INTERLEUKIN-6 (IL-6)-DEPENDENT AND IL-6-INDEPENDENT MULTIPLE-MYELOMA CELL-LINES/

A poor response to Fas-induced apoptosis is evident in same multiple m yeloma (MM) cell lines and primary cells. In this study, we have exami ned the possibility to increase the sensitivity to Fas-induced apoptos is by pretreatment of MM cells with interferon-gamma (IFN-gamma) or in terferon-alpha (IFN-alpha). Both IFN-gamma and IFN-alpha markedly incr eased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-2958 cell lines, pret reatment with either IFN-gamma or IFN-alpha also inhibited proliferati on in a dose-dependent manner. In contrast, IFN-gamma activation of th e Fas death pathway in the U-266-1984 cells was not accompanied by gro wth inhibition. Incubation with the IFNs increased the Fas antigen exp ression in one of th ree cell lines but did not alter the expression o f Bcl-2 or Bax. The IFNs are important regulators of growth and surviv al in MM cells. Our results suggest that activation of Fas-mediated ap optosis is a novel mechanism by which the IFNs exert inhibitory effect s on MM cells. (C) 1998 by The American Society of Hematology.