Statin-sensitive primary patient MM cells express lower levels of HMGCR and show a lack of its up-regulation on statin exposure. Mononuclear cells freshly isolated from bone marrow aspirates were cultured in the presence of a vehicle control, 20μM lovastatin, or 20μM atorvastatin. After 16 hours, a portion of the sample was sorted for the CD138⁺ MM population, and RNA was harvested for cDNA synthesis and real-time PCR. (A) The remainder was exposed to statin or control for a total of 48 hours before being labeled with anti-CD138–phycoerythrin and fluorescein isothiocyanate–conjugated annexin V for apoptosis analysis. Two samples were identified as being sensitive to statin-induced apoptosis by a decrease in the viable CD138⁺ MM population (top left quadrant) and 3 were insensitive; representative samples are shown. (B) Real-time PCR was used to assess the expression of HMGCR-FL, HMGCR-D13, and HMGCS1, all measured relative to GAPDH. Data represent individual measurements.