BCL-2, BAX AND P53 EXPRESSION IN B-CLL IN RELATION TO IN-VITRO SURVIVAL AND CLINICAL PROGRESSION

Our previous data have shown that isolated leukemic cells from progres sive chronic lymphocytic leukemia (B-CLL) patients respond to growth s timulation in vitro and express high levels of p53, immunoreactive wit h the configuration-specific antibody PAb 240. We have now analyzed th e in vitro survival of B-CLL cells in relation to Bcl-2, Bax(alpha) an d p53 expression and compared this with the clinical progression of th e disease. Leukemic cells from patients with progressive disease demon strated higher in vitro survival, compared with non-progressive B-CLL and normal B cells. All cells were sensitive to treatment with a combi nation of glucocorticoid and cAMP. Bcl-2 protein levels were not relat ed to clinical progression, as measured by flow cytometry. Competitive PCR showed that Bcl-2 mRNA was over-expressed in most of the B-CLL sa mples and that p53 mRNA expression was similar between B-CLL groups an d normal values and thus not related to clinical progression. However, since Bax(alpha) expression was lower in progressive than in non-prog ressive patients, the Bcl-2/Bax(alpha) ratio at the mRNA level was sig nificantly higher in the progressive group. Our data suggest that the Bcl-2/Bax(alpha) ratio is important for the regulation of B-CLL cell s urvival, that p53 over-expression in progressive B-CLL is the result o f post-transcriptional modifications and that a directed PKA activatio n may potentiate the cytolytic effect of glucocorticoids in vivo. (C) 1996 Wiley-Liss, Inc.