APO-1 MEDIATED APOPTOSIS OR PROLIFERATION IN HUMAN CHRONIC B-LYMPHOCYTIC LEUKEMIA - CORRELATION WITH BCL-2 ONCOGENE EXPRESSION

We studied induction of apoptosis in several human malignant B cells from chronic lymphocytic leukemias (BCLL) by triggering the APO-1 antigen. The APO-1 antigen was found to be expressed on the surface of malignant B cells. In BCLL cells from most patients, APO-1 antigen expression increased following in vitro activation by Staphylococcus aureus Cowan I (SAC) or interleukin-2 (IL-2). In certain cases of BCLL co-stimulation with SAC plus IL-2 resulted in a synergistic up-regulation of the APO-1 antigen on the cell surface and prepared BCLL cells for monoclonal antibody anti-APO-1 mediated apoptosis. Interestingly, bcl-2 mRNA expression decreased upon stimulation with SAC plus IL-2, whereas SAC or IL-2 alone did not affect the level of bcl-2 expression.Thus, in these BCLL cells induction of anti-APO-1-mediated apoptosis appeared to be correlated with bcl-2 mRNA down-regulation. One informative BCLL, however, with a similar pattern of APO-1-antigen expression, did not show SAC plus IL-2-dependent bcl-2 down-regulation. Surprisingly, these cells proliferated in response to anti-APO-1 only when cells were co-stimulated with SAC plus IL-2. Our data suggest that down-regulation of bcl-2 prepares BCLL cells for induction of APO-1-mediated apoptosis. In addition they demonstrate that triggering of the APO-1 antigen may also lead to the induction of proliferation in special cases of BCLL.