WM cells harboring the C1013G/CXCR4 somatic variant present with drug resistance. (A) GSEA enrichment plots of multiple drug resistance and response to drug signature genes in C1013G/CXCR4-mutated cells and control vector–infected cells (control cells), respectively. The green curves show the enrichment score and reflects the degree to which each gene (black vertical lines) is represented at the top or bottom of the ranked gene list. The heat map indicates the relative abundance (red to blue) of the genes specifically enriched in the mutated cells as compared with the control cells. Gene sets were considered enriched with an FDR always <0.25. Normalized enrichments score (NES) and FDR are shown per each gene set analyzed. (B-F) C1013G/CXCR4 WM cell lines (BCWM1; MWCL1) or control vector–infected cells (control) were exposed to everolimus, ibrutinib, idelalisib, bortezomib, and carfilzomib for 48 hours. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.