The Baxα:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia

Abstract

Bcl‐2 over‐expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Baxα to Bcl‐2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Baxα‐to‐Bcl‐2 ratio as assessed by Western‐blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbaxα‐transfected CEM C7 clones, a similar correlation was found for dexamethasone and thapsigargin sensitivity. In bone‐marrow aspirates from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n = 48; AML, n = 8), the Bcl‐2 and Baxα levels were highly variable, but well within the range found in the Baxα transfectants and in the established cell lines. Bcl‐2 levels were lower in T‐ than in B‐lineage ALL, which could be ascribed to simultaneous inverse relation between Bcl‐2 and WBC. By contrast, Baxα:Bcl‐2 was independent of any presenting feature and was largely dependent on Baxα levels. Results suggest that Baxα:Bcl‐2, rather than Bcl‐2 alone is important for the survival of drug‐induced apoptosis in leukemic cell lines and ALL. Int. J. Cancer 71: 959‐965, 1997. © 1997 Wiley‐Liss Inc.