Figure 2.
Effects of carfilzomib on cell viability in models of imatinib-sensitive and -resistant CML. (a) Viability of CML cell lines following 24 h culture with increasing doses of carfilzomib (1–1000 nM). (b) Viability of CML cell lines following 1 h exposure to increasing doses of carfilzomib (1–1000 nM); cells were pulsed with carfilzomib followed by culture in drug-free medium for 24 h. Cell lines are grouped as parental imatinib-sensitive cell lines alongside their imatinib-resistant counterparts. (c) Viability of CML CD34+38− cells and normal CD34+38− cells exposed to 50 nM carfilzomib for 1 h followed by 24 h growth in drug-free medium. Viability of CML CD34+38− was significantly reduced compared with NBM (P=0.02). (a–c) All results are expressed as percentage of untreated control and represent mean±s.d. (n=3). (d) CML (n=3) and normal (n=2) CD34+ cells were exposed to 50 nM carfilzomib followed by long-term culture in LTC-IC assays. Results are expressed as percentage of control colony count and represent mean±s.d. There was significantly less colony growth in CML LTC-IC compared with NBM (P=0.04). (e) Western blot analysis for activated (cleaved) caspase-8 and caspase-9 following exposure to carfilzomib.
