IL4R mutations led to CCL17 and CD23 expression as part of a PMBCL-characteristic phenotype. (A) Differential gene expression of RNA isolated from doxycycline-treated DEV IL4R^WT and IL4R^I242N cells by RNA-Seq. The most significantly changed genes are shown (Q value ≤ 0.01). (B-C) Transduced DEV cells with retrovirus control (empty) or retrovirus expressing IL4R WT or I242N mutant under control of doxycycline (20 ng/mL, 48 hours) were treated with human recombinant IL-4 (20 ng/mL) for 24 hours or left UT. (B) CCL17 released in supernatants by transduced DEV cells was measured by ELISA. (C) Flow cytometry analysis of cell-surface expression of CD23 represented as bar plot. (D-E) GSEA of the differential gene expression obtained from specimens overlapped with PMBCL gene-expression signature described in Rosenwald et al.³  is represented as waterfall plot (D) and GSEA enrichment plot (E). (B-C) Graphs show the mean ± SD of 3 (B) or 4 (C) independent experiments and significance evaluated using 2-sample 2-tailed Student t test. *P < .05; **P < .01. ES, enrichment score; FDR, false discovery rate; GSEA, gene-set enrichment analysis; NES, normalized enrichment score.