Bax is frequently compromised in Burkitt's lymphomas with irreversible resistance to Fas-induced apoptosis

We have analyzed the Pas-mediated death pathway in a panel of ii Epstein-Ba rr virus (EBV)-negative and 10 EBV-positive Burkitt's lymphoma (BL) cell li nes. We show that the increased expression of Fas in EBV-positive cell line s is mediated via LMP-1. Four of the 21 BL cell lines are readily responsiv e to Pas-mediated cell death signals. Of the remaining 17 cell lines, 10 ca n be sensitized by up-regulating Pas either via exogenous expression of LMP -I or via treatment with CD40L. These same cell lines can also be sensitize d by treatment with cycloheximide (CHX), which, however, does not result in up-regulation of Pas. Neither up-regulation of Pas, nor treatment with CHX , restore Fas sensitivity in seven BL cell lines. Further analyses indicate d that 5 of the 7 cell lines land none of the 14 responsive cell lines) wer e also compromised in the integrity/expression of the proapoptotic gene Bax . Thus, in most BL cell lines, the Fas pathway seems to be inhibited, altho ugh the mechanism of inhibition varies. The correlation between Bar mutatio n and irreversible (by CD40L or CHX) Pas resistance raises the possibility, for the first time, that Bas may play a critical function in Pas-mediated cell death in BL.