Treatment of PEL cell lines with lenalidomide and pomalidomide leads to degradation of neosubstrates IKZF1, IKZF3, ZFP91, and CK1α in a CRBN-dependent manner. (A) IC₅₀ curves in parental BC-3 or a BC-3 clone with CRISPR-inactivated CRBN (n = 3; error bars represent standard error of the mean). Inset: western blot analysis of BC-3 and the CRBN knockout (KO) clone. (B-C) Quantitative western blot analysis of CK1α, ZFP91, IKZF1, IKZF3, and IRF4 expression at the indicated time points after treatment of BC-3, BCBL-1, or BC-3 CRBN KO cells with 10 μM of lenalidomide (B) or 1 μM of pomalidomide (C). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) served as loading control. Supplemental Figure 1 shows growth curve and quantitative analysis. WT, wild type.