REGULATION OF CLINICAL CHEMORESISTANCE BY BCL-2 AND BAX ONCOPROTEINS IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

The bcl-2 gene was first shown to be dysregulated in the majority of f ollicular lymphomas in which a t(14;18) chromosomal translocation is p resent, but is also over-expressed in the absence of gene rearrangemen ts in most cases of B-cell chronic lymphocytic leukaemia (B-CLL). The bcl-2 oncoprotein is a regulator of apoptosis and the activity of this protein is opposed by bar, a homologous protein that accelerates the rate of cell death. B-lymphocyte bcl-2 and bar protein levels were fou nd to be significantly altered in B-CLL patients when compared to thos e of a normal control group. Increased bcl-2/bax ratios were observed in both the treated and untreated patients when compared to those of n ormal controls. These alterations were particularly pronounced in thos e treated patients found to be clinically unresponsive to chemotherapy .