Microarray analysis reveals distinct differences in mRNA levels in response to lovastatin in sensitive and insensitive MM cells. Three independent biologic replicates of KMS11, H929, LP1, and SKMM1 cells were exposed to 20μM lovastatin or a vehicle control for 16 hours before being harvested for mRNA abundance profiling by microarray. (A) The entire dataset was visualized using unsupervised machine learning. The resulting heatmap demonstrates that global expression patterns of the sensitive cells were much more similar to each other than to insensitive cells. (B) Six MVA pathway genes, including HMGCR, are plotted from the microarray to show that all were up-regulated in both LP1 and SKMM1, but not substantially in KMS11 and H929 cells, in response to lovastatin exposure. **P < .0001 (model-based t test with Bayesian moderation of SE and false discovery adjustment). Results were validated by real-time PCR for both HMGCR (C) and HMGCS1 (D), measured relative to GAPDH. *P < .05 (Student t test with Welch adjustment for multiple testing comparing ethanol with lovastatin treatments). (E) MM cells were exposed to 20μM lovastatin or a vehicle control for 24 hours before being harvested for protein lysates. Immunoblots were probed with anti-HMGCR and antitubulin as a loading control. All experiments were performed a minimum of 3 times. Data are mean ± SD.