FIGURE 2.

MMCLs are sensitized to BH3 mimetics by simvastatin. We assessed a panel of seven myeloma cell lines including: OPM2, L363, KMS-12-PE, NCI-H929, MOLP8, RPMI-8226, and U266. A, Representative plots of statin-sensitive (black) MMCLs are shown alongside statin insensitive (red). The initial screen used PI exclusion to determine viability by flow cytometry. Rescue with 1 mmol/L mevalonate was demonstrated at the highest concentration of simvastatin to demonstrate on-target activity. Of note, statin-mediated killing of RPMI-8226 is not fully rescued by mevalonate, perhaps due to inefficient cellular uptake. n = 3, error bars indicate SD. B, IC₅₀ of venetoclax or C, S63845 at concentrations of statins necessary to significantly shift the IC₅₀. Significance (P value <0.05) was determined by extra sum-of-squares F test for differences in log IC₅₀. Achieving significance was the classification determinant for statin-sensitive and statin-insensitive cell lines. *, P < 0.05; **, P < 0.01; *** , P < 0.001; ****, P < 0.0001 of Bonferroni-adjusted P values.