Preclinical evaluation of apoptosis induction by the novel small molecule BCL-2 inhibitor, GX015–070, in ex vivo chronic lymphoid leukemia (CLL) cells

3149 Background: CLL is associated with loss of normal cellular apoptotic function. Apoptosis in cell lines has been identified with GX015–070 (GX), a small molecule antagonist of the BH3-binding groove of the BCL-2 family of proteins which is frequently overexpressed in cancers including CLL. This study evaluated GX induced apoptosis in CLL cells ex vivo correlating it with prognostic factors. Methods: Circulating lymphocytes were collected from patients (pts) with ≥ 20x109/L lymphocytes with no CLL treatment or red cell transfusions within 4 wks. Medical history was recorded. The diagnosis was confirmed with immunophenotyping by flow cytometry. CD38 was assessed in this analysis. The cytogenetic abnormalities del(11q), +12, del(13)(q14.3), del(13)(q34) & del(17p) were established by fluorescent in situ hybridization. Apoptosis was assessed with surface annexin V immunophenotyping in B cell enriched samples with positive glucocorticoid and negative DMSO controls. Results: 30 pts were recruited including ...