BCL-2 EXPRESSION IN CHRONIC LYMPHOCYTIC-LEUKEMIA AND ITS CORRELATION WITH THE INDUCTION OF APOPTOSIS AND CLINICAL OUTCOME

Transcriptional deregulation of the Bcl-2 gene has been demonstrated t o extend cell viability via an inhibition of apoptotic cell death. Chr onic lymphocytic leukemia (CLL) cells are inherently susceptible to ap optosis during short-term culture. Because increased expression of the Bcl-2 gene has been reported in CLL, we sought to correlate Bcl-2 pro tein expression with the in vitro propensity towards apoptosis and als o clinical outcome. Immunoblot analysis of Bcl-2 protein revealed inte rpatient variability with nine of 42 (21%) cases demonstrating similar or greater expression than a t(14;18) containing lymphoma cell line a nd 18 of 42 (43%) cases demonstrating a level of expression similar to or less than that seen in normal peripheral blood lymphocytes. Bcl-2 expression did not correlate with clinical features, or with apoptosis , as measured by an in vitro DNA fragmentation assay. However, analysi s of survival in the 33 untreated patients revealed significant differ ences based on the level of Bcl-2 expression, with higher expression b eing an adverse feature (P < 0.02). This data suggests that Bcl-2 is i mportant in the pathogenesis and progression of CLL and that quantitat ion of Bcl-2 protein may provide useful prognostic information.