Lymphoma cells with BCL2/PMAIP1 coamplification are highly sensitive to BCL-2 inhibitor. Lymphoma cells with BCL2/PMAIP1 coamplification are highly sensitive.

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Lymphoma cells with BCL2/PMAIP1 coamplification are highly sensitive to BCL-2 inhibitor. Lymphoma cells with BCL2/PMAIP1 coamplification are highly sensitive to BCL-2 inhibitor. (A) Dose–response curve showing the effect of pharmacological inhibition of BCL2 on lymphoma cells. Cells were incubated with S55746 from 0.01 μM to 10 μM for 72 h. Cell viability was determined by MTS assay. Cells are color-coded by tumor types (ABC DLBCL in red, GCB DLBCL in blue, MCL in green, HL in purple, and BL in black). Error bars represent SEM of triplicate experiments. (B) Correlation between the IC50 concentrations (mean ± SEM) and genetic alterations in lymphoma cell lines. The two most sensitive cell lines (U-2932 and Ri-1) harbored BCL2 and PMAIP1/NOXA gene amplifications. (C and D) In vivo activity of S55746 in two DLBCL lymphoma xenograft models. (C) Ri-1 (NOXA amplification) and (D) HBL-1 (no NOXA amplification). Mice were treated with S55746 or vehicle (intravenously) at 50, 75, or 100 mg/kg, once a day for 3 wk. Tumor volume was measured three times per week. S55746 strongly inhibits tumor growth in Ri-1 but not in HBL-1. Differences among groups were calculated with the ANOVA Dunnett’s test. ****P < 0.00001. Yuxuan Liu et al. PNAS 2018;115:47:12034-12039 ©2018 by National Academy of Sciences