Fig. 4

BrdU analysis of cell-cycle kinetics in MOLM-13 and MV4-11 cells treated with idasanutlin and venetoclax alone and in combination for 72 h. BrdU was added for the last 24 h of the experiment as described in the “Methods” section. Populations residing in G1, S, and G2/M phases are indicated as an example for MOLM-13 vehicle-treated cells. Sub G1 represents nuclear fragmentation as a consequence of cell death. Vehicle (DMSO)-treated cells displayed normal proliferation, with MOLM-13 cells reaching the third and MV4-11 cells reaching the second cycle. Treatment with idasanutlin induces cell cycle arrest and minor nuclear fragmentation from the G1 phase of the second cell cycle (sub G1, arrows). Treatment with venetoclax did not affect cell cycle progression, but induced nuclear fragmentation mainly from the G1 phase of the first cycle (arrows). Combination treatment results in remarkably enhanced nuclear fragmentation from the G1 phase of the first cell cycle onwards with few viable cells remaining