Microenvironment-dependent loss of mitochondrial priming and acquired drug resistance in primary MCL cells. (A) BH3 profiling of primary MCL from 4 patients and Maver-1 cells performed as described in “Methods.” Values for Maver-1 cells are the mean of 3 independent experiments. (B-C) Primary MCL cells freshly isolated from PB (−) or after 7 days on an L-40L or hMSC layer in the presence of cytokines were cultured with VNT (25 nM), bendamustine (BDM; 50-100 µM), or BTZ (10-20 nM) for 24 hours. Viability was then addressed by annexin-V staining, the % of live cells is represented as the % of control (without treatment). ****P < .0001; paired Student t test. (D) siRNA against BCLXL reduced Bcl-x_L protein expression and impaired L-40L–induced protection against BDM (24 hours, 100 µM) or VNT (24 hours, 50 nM) cytotoxicity in Maver-1 cells. *Lower exposure. Representative western blot of 3 experiments.