CRISPR-Cas9 inactivation-based CM resistance screens in the PEL cell line BC-3. (A) Schematic of the CM-bound CRL4^CRBN E3 Ub ligase complex. (B) Experimental outline of CM resistance screens. (C) Cumulative live cell counts of BC-3/Cas9 during the duration of the screens. Cell numbers were normalized to those from dimethyl sulfoxide (DMSO)–treated control cells. Arrows indicate early and late points at which a subset of cells were taken from the pool for analysis of sgRNA distribution. (D) Absolute live cell counts of LEN, POM, or CC-122–treated BC-3/Cas9 cells at late times in the screen shows emergence of proliferating cell pools under continued drug treatment.