Fig. 5. Cellular respiration, BCR signaling and OXPHOS inhibition in RT cells.

a, Oxygen consumption of intact CLL and RT cells of three patients at routine respiration (routine), oligomycin-inhibited leak respiration (uncoupled) and uncoupler-stimulated ETC. Each dot represents a technical replicate. The mean of the replicates is shown using a horizontal line (left). Summary of the routine respiration of CLL and RT cells of the three patients collapsed (right). b, Calcium kinetics of tumoral cells (CD19⁺, CD5⁺) upon stimulation with 4-hydroxytamoxifen (4-OHT) and anti-BCR (black arrow). Basal calcium was adjusted at 5 × 10⁹ Indo-1 ratio for 60 s before cell stimulation with F(ab′)2 anti-human IgM + H₂O₂ at 37 °C. Then, Ca²⁺ flux was recorded up to 500 s (left). Summary of the calcium release after BCR stimulation of CLL and RT cells. Average mean fluorescence after stimulation is represented (right). c, Cell proliferation after 72-h incubation with or without IACS-010759 (IACS) at 100 nM. Percentage of proliferating cells was determined by carboxyfluorescein succinimidyl ester (CFSE) cell tracer. Two technical replicates of each sample were performed (left). Summary of the proliferation for each CLL and RT cells with or without IACS treatment after 72 h. The normalized percentage of growth inhibition is indicated (right).