FIGURE 6.

Pitavastatin-mediated activation of the ISR induces NOXA to sensitize to venetoclax separately from PUMA. Heat map summary of BCL2 family Western blot screen across all statin-sensitive cells (NCI-H929, MM.1S, L363, OPM2, MOLP8, and KMS12PE) for 16 (A) and 40 hours (B) treatments with 1 µmol/L pitavastatin. log₂ transformed mean fold change of three replicates of each MMCL are plotted on a double gradient scale. C, Western blot analysis of the t(4;14) OPM2 and non-t(4;14) MM1S treated with 1 µmol/L pitavastatin or pitavastatin/ISRIB. NOXA upregulation is partially blocked by ISRIB, but PUMA is mostly ISR independent. Representative of n = 2 for tested cell lines. D, The apoptosis sensitizing effects of pitavastatin are blocked in BBC3 (PUMA) knockout L363 cell line treated with ISRIB in a 40-hour Annexin V-PI viability assay, n = 4.