Validation of candidate genes modulating ALK TKI sensitivity in ALCL patients. (A) Schema of the treatment history of ALK+ ALCL patients who relapsed on ALK-targeted therapy (patients 1 and 2) or chemotherapy (patients 3 and 4). (B) Unsupervised clustering of RNA-seq data from chemotherapy-relapsed (patients 3 and 4) and ALK TKI–resistant (patients 1 and 2) patients. (C) Principal component (PC) analysis of gene-expression levels across the 4 resistant ALCL patient samples. (D) Candidate genes identified by the CRISPR screens were analyzed for differential expression between ALK TKI–resistant patients with wild-type or mutated ALK. ALCL99*, patient was treated according to ALCL99 recommendations for patients with central nervous system involvement, as specified in Williams et al.78 CPM, counts per million.