Generation of acquired ibrutinib-resistant DLBCL cells and clonogenic properties. (A) Ibrutinib-resistant DLBCL cell lines were generated from parental (PT) lines as described in “Materials and methods.” The percentage of cell survival and total apoptosis were determined after 72 hours of ibrutinib treatment. (B) DLBCL cell growth rates were determined by proliferation assay; we counted cells for 7 days and compared their growth rates with growth rates of respective PT lines. (C) Representative images and quantification data from colony formation assays. (D) OCI-LY10 tumor cells (parental/ibrutinib-resistant [PT/IR]) suspended in a 1:1 Matrigel mixture were implanted subcutaneously into nude mice (n = 14). Twenty days after injection, tumor volumes were measured. Compared with the tumors in the PT group, tumors in the IR DLBCL group were larger (P<.0001). Error bars represent standard error. **P < .01; ***P < .001.