Genome-wide CRISPR library screens identify the IL-1R pathway as a novel oncogenic driver in pC-ALCL. (A) Outline of the workflow of the depletion CRISPR library screens in lymphoma cell lines (upper). Overview of the genome-wide CRISPR screen results (lower). Shown are the volcano plots of all genes in 2 lines. y-axis indicates the significance (−log₁₀p); x-axis indicates the log₂ fold change (sgRNA on/off). The dashed lines indicate P = .05 and log2(FC) = ±4. (B) Top significantly enriched cellular pathways identified among the oncogenic hits identified from MAC1 or Karpas299 genome-wide CRISPR screens [log₂(fold change) < −4 and P < .05] in panel A. (C) Left, diagrammatic representation of the workflow for the sgRNA toxicity assay. Right, ALCL lines were transduced with IRAK1, MYD88, IL1R1, IL1RAP, or control sgRNAs along with green fluorescent protein (GFP). The fraction of viable GFP+/sgRNA+ cells relative to the live cell fraction is plotted at the indicated times after sgRNA induction, normalized to day 0 values. Error bars denote standard deviation (SD) of triplicates. P was calculated comparing day 0 to each time point of indicated sgRNA induction in MAC1 and MAC2A lines. ∗∗P < .01.