Multi-Agent Chemotherapy Overcomes Glucocorticoid Resistance Conferred by a BIM Deletion Polymorphism in Pediatric Acute Lymphoblastic Leukemia
Figure 2
The BIM deletion confers dexamethasone resistance in CCRF-CEM cells.
(A) Cell viability following exposure of CCRF-CEM subclones to increasing concentrations of dexamethasone. Viability was measured by MTS assay at 48 h. Error bars indicate mean ± SEM (n = 3) of 3 independent replicates. (B) Western blot of cell lysates from CCRF-CEM BIMi2+/+, BIMi2+/− and BIMi2−/− clones following treatment with increasing doses of dexamethasone for 48 h. The induction of cleaved PARP and cleaved caspase 3 were used as readouts for apoptosis. An antibody that recognizes pro-apoptotic exon-4 containing BIM isoforms (BIM EL, L and S) was used to show the extent of BIM upregulation following GC exposure. β-actin was used as a loading control. (C) Western blot showing phosphorylation of the glucocorticoid receptor (Phospho-GR S211) in CCRF-CEM BIMi2+/+, BIMi2+/− and BIMi2−/− clones upon treatment with dexamethasone.