A Genome-wide CRISPR screening reveals candidate CC-122 resistance genes in DLBCL. (A) The genome-wide CRISPR screening of SU-DHL-4 cells. (B) Scatter plot of genes with a log2FC (T10_CC-122 vs T10_DMSO) >0 and false discovery rate (FDR) <0.05; x-axis: gene essentiality score shown as log2FC (T10_DMSO vs T0_DMSO); y-axis: resistance score shown as log2FC (T10_CC-122 vs T10_DMSO). Brown open circles mark resistance genes common to other cereblon modulators. Red solid circles mark novel resistance genes unique to CC-122. (C) Log2FC (T10_CC-122 vs T10_DMSO) values of sgRNAs targeting CC-122–enriched genes. Blue represents the background distribution of the sgRNA library, and each vertical line represents an individual sgRNA (5-8 per gene). (D) Pathway enrichment analysis of genes enriched by CC-122 treatment, with log2 FC >1 and FDR <0.05 relative to DMSO control. The color and size of the dots represent the adjusted significance level and gene ratio, respectively. Gene ratio refers to the number of input genes annotated to an individual pathway as a ratio of all input genes annotated to any Reactome database pathway.