Carfilzomib and chemotherapeutic resistance. (A) ANBL-6.BR cells, and their wt counterparts, were pulsed with carfilzomib for 1 hour, and proliferation was assessed using the WST-1 reagent after a 24-hour recovery period. The DOR to bortezomib was computed by comparing the IC₅₀ of bortezomib-sensitive and BR cells. (B) CD138⁺ cells from a MM patient with a chromosome 13 deletion who did not have a clinical response to bortezomib were treated with continuous exposure to the indicated concentrations of carfilzomib or bortezomib for 24 hours in triplicate, followed by measurement of proliferation with the WST-1 assay. (C) CD138⁺ cells from a MM patient who progressed while on bortezomib treatment were exposed to increasing concentrations of carfilzomib or bortezomib for 24 hours before assessment for cellular proliferation. (D) CD138⁺ plasma cells from a patient who progressed on bortezomib were exposed to continuous and pulse treatments with equivalent concentrations of carfilzomib and bortezomib, followed by a WST-1 cellular proliferation assay. (E) RPMI 8226 cells were treated continuously with 5 nM carfilzomib and 10 μM Dex for 48 hours to determine the effect of this combined therapy against cellular proliferation. Error bars are SD.