BCL-2 BAX RATIOS IN CHRONIC LYMPHOCYTIC-LEUKEMIA AND THEIR CORRELATION WITH IN-VITRO APOPTOSIS AND CLINICAL RESISTANCE/

The bcl-2 gene is overexpressed in the absence of gene rearrangements in most cases of B-cell chronic lymphocytic leukaemia (B-CLL) and the proto-oncogene product Bcl-2 has been shown to be a regulator of apopt osis. The activity of this protein is opposed by Bar, a homologous pro tein that accelerates the rate of cell death. B-lymphocyte Bcl-2 and B ar protein levels were found to be significantly altered in B-CLL and increased Bcl-2/Bax ratios were observed in both the treated and untre ated patients compared with those of normal controls. These alteration s were particularly pronounced in those treated patients found to be c linically unresponsive to chemotherapy. In order to determine whether Bcl-2/Bax ratios affected cell survival via an anti-apoptotic mechanis m, cell death was induced in B-CLL cells in vitro using chlorambucil, and apoptosis was monitored by Annexin V and propidium iodide staining . Confirmation that the labelled cells were apoptotic was achieved by morphological assessment of cytospin preparations of cell-sorted popul ations. Drug-induced apoptosis in B-CLL cells was inversely related to Bcl-2/Bax ratios.