The Baxα:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia
✍ Scribed by Gajja S. Salomons; Hugh J.M. Brady; Manon Verwijs-Janssen; Joop D. Van Den Berg; Augustinus A.M. Hart; Henk Van Den Berg; Henk Behrendt; Karel Hahlen; Lou A. Smets
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 109 KB
- Volume
- 71
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Baxa 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 Baxa-to-Bcl-2 ratio as assessed by Western-blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbaxa-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 5 48; AML, n 5 8), the Bcl-2 and Baxa levels were highly variable, but well within the range found in the Baxa 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, Baxa:Bcl-2 was independent of any presenting feature and was largely dependent on Baxa levels. Results suggest that Baxa:Bcl-2, rather than Bcl-2 alone is important for the survival of drug-induced apoptosis in leukemic cell lines and ALL.