Mitochondrial dependence of drug-induced p53 accumulation in activated T cells and primary leukemia. Normal PB T cells and ALL cells were incubated with oligomycin (10 μg/mL) and/or etoposide (30 μM) for 6 hours and assessed for MTMP and p53 levels. (A) MTMP (JC-1 fluorescence, 4-decade log scaling) is increased in activated T cells and is down-regulated by oligomycin (10 μg/mL). (B) Oligomycin prevents etoposide-induced p53 accumulation in activated T-cells. ▧ indicates medium; ▪ indicates etoposide; ▦ indicates etoposide plus oligomycin. (C) Heterogeneous sensitivity to etoposide and to oligomycin in a series of ALL samples. Each individual leukemic sample is presented as a point, positioned according to the value of drug-specific p53 accumulation in the presence (y-axis) and absence (x-axis) of oligomycin. (D) Constitutive MTMP levels correlate with p53 drug sensitivity in a series of ALL samples (Spearman analysis: r_s = 0.68, P < .05).