PLX51107 and PLX2853 BETi effectively combine with ABT199 in DHL/DEL cell lines. (A) SUDHL6, DOHH2, and OCI-LY-8 were treated with 1000 nM PLX5, 100 nM PLX2, or a vehicle control (Con) alongside 600 nM ABT199 or an additional vehicle control (DMSO) for 48 hours, and viability was assessed by annexin V/PI staining. (Bi) SUDHL6 was subjected to a dose titration of PLX5 or PLX2 in the presence of increasing ABT199 concentrations and assessed for viability after 48 hours by annexin V/PI staining. Doses (0 nM) represent the addition of an appropriate DMSO vehicle control. (Bii) SUDHL6 data were assessed for synergy using the Chou-Talalay method and CompuSyn software. Points are color coded according to PLX5/PLX2 dose depicted in panel i. Data represent the average of triplicate data. (C) SUDHL6 were transduced with empty vector (GFP) or shBIM constructs, and BIM protein expression was assessed by western blotting (i). The impact of BIM knockdown on the combination of BETi and ABT199 was then assessed by treating SUDHL6 GFP/shBIM as described in panel A. Error bars represent SEM. Statistical analyses were performed using 2-way ANOVA and Dunnett’s multiple comparison tests. **P < .005, *P < .05. Fa, effect; CI, combination index.