PMAIP1/NOXA gene amplification increases DLBCL vulnerability to BCL2 inhibitors. PMAIP1/NOXA gene amplification increases DLBCL vulnerability to BCL2 inhibitors.

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PMAIP1/NOXA gene amplification increases DLBCL vulnerability to BCL2 inhibitors. PMAIP1/NOXA gene amplification increases DLBCL vulnerability to BCL2 inhibitors. (A) Representative FISH staining in U-2932 and Ri-1 cells demonstrating an increase BCL2 (red) and PMAIP1/NOXA (green) copy numbers. Centrosome of chromosome 18 is shown in light blue. (Magnification: 63×.) (B) NOXA genetic silencing attenuates S55746 activity in Ri-1 DLBCL cells. Ri-1 cells were transfected with 1 μM scramble or PMAIP1/NOXA siRNA and incubated with increasing concentrations of S55746 (0.1, 0.25, and 0.5 μM). (C) Cell viability was assessed for cells in B by MTS assay after 48 h. Error bars represent SEM of triplicate experiments. Differences between groups were calculated with the Student t test. ***P = 0.005, ****P < 0.0001. (D) NOXA ectopic overexpression enhanced the efficacy of S55746 in HBL-1 DLBCL cells. (E) Cell viability was assessed for cells in D by MTS assay after 48 h. Viability data were normalized to effect of NOXA overexpression alone. Error bars represent SEM of triplicate experiments. *P < 0.05, ***P < 0.0005. Yuxuan Liu et al. PNAS 2018;115:47:12034-12039 ©2018 by National Academy of Sciences