Negative cell cycle control of human T cells by beta-galactoside binding protein (beta GBP): Induction of programmed cell death in leukaemic cells

The cell cycle is negatively regulated by diverse molecular events which or iginate in part from the interaction of secreted proteins with specific cel l surface receptors. By exerting negative control on cell proliferation, th ese factors can help maintain cell number balance both through growth restr aints and the induction of apoptosis and may thus contribute to prevent or control tumourigenesis. Here we report that beta GBP, a negative growth fac tor which controls transition from S phase into G(2), Causes an S/G(2) grow th arrest in both normal and leukaemic T cells. However, in leukaemic T cel ls but not in normal T lymphocytes, growth arrest is followed by apoptosis. Analysis of possible mechanisms of induction of apoptosis does not support Fas and Fas L as having a main role but points instead to Bcl-2 and Bar. T he induction of apoptosis in leukaemic T cells is characterised by the decr ease of Bcl-2 and consequent predominance of Bar. By contrast, in the norma l T cells, which do not enter apoptosis, the quantitative relationship of B cl-2 to Bar remains unchanged. The ability of beta CBP to selectively induc e apoptosis in leukaemic cells suggests that beta CBP may play a role in ca ncer surveillance and that its use has potential therapeutic implications. (C) 1999 Wiley-Liss, Inc.