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. Author manuscript; available in PMC: 2014 May 1.
Published in final edited form as: Clin Cancer Res. 2013 Mar 20;19(9):2406–2419. doi: 10.1158/1078-0432.CCR-12-2754

Figure 5. Carfilzomib is cytotoxic to CLL cells independent of p53.

Figure 5

CLL cells were treated with CFZ (300 nM) for 1 hr and whole cell lysates were collected at 8 hr. Gamma irradiation (5 Gy) was included as a positive control for p53-dependent treatment. Untreated and UV-irradiated Jurkat cells were included as negative and positive controls for expression of Noxa protein. Changes in p53 and its targets were assessed by (A) immunoblot (n=6) and (B) real-time RT-PCR (n=6–14). CFZ treatment induced p21 (*p<0.0001) and PUMA (**p=0.0323) and significantly down regulated p53 by 0.75 fold (***p=0.0193) compared to vehicle. Horizontal lines represent the geometric mean. (C) CLL samples from patients with or without del(17p13.1) (n=9) were incubated with 100 and 300 nM of CFZ for 1 hr. No significant differences were observed (p=0.3924). 5 Gy Gamma irradiation and fludarabine (Fara A) were included as controls for p53-dependent treatments and were more cytotoxic in non-del(17p13.1) patients than del(17p13.1) patients (*p<0.0001,** p=0.0002). Viability was determined by annexin V/PI flow cytometry at 24 hr. Horizontal lines represent the mean.