Pleri antagonizes chemokine-induced and ibr-driven cell internalization. (A) Labeled FSCCL cells were treated with CM and pleri or DMSO as indicated for 24 hours; CXCL, CM from CXCL12/13-BMF; Ctrl, CM from untransduced BMF. Pleri was added at 1 μM, and CIC counting was conducted at 24 hours after the CM/drug addition. Each of 3 experiments was represented by 1 dot. Data were analyzed with paired, parametric, 2-tailed t test. (B) FSCCL cells were treated as indicated in the absence of CM. Ibr was added at 0.4 μM and Pleri at 1 μM. CIC counting was conducted 24 hours after the drug addition. Each of 5 experiments was represented by 1 dot. (C) CXCR4 in FSCCL cells were knocked out using gRNA1 (KO1) and gRNA2 (KO2). CIC counting conducted was conducted at 5 hour after coculture. (D) Primary CLL cells (n = 7) were treated similarly to the cell line. Each dot represents a sample; black lines represent ibr-sentive sample; blueline, ibr-resistant sample. Data were analyzed with paired, parametric, 2-tailed t test. (E) Cartoon that summarized our key findings; (a) shows ibr driving CLL cells into BM fibroblasts (CIC); (b), the chemokine CXCR4-CXCL12 axis mediates this process; (c), the CXCR4 antagonist pleri blocks ibr-driven CIC. Ctrl, control.