R406 antagonizes the increased chemotaxis and migration beneath marrow stromal cells (pseudoemperipolesis) of CLL cells after BCR triggering. (A) Displayed are bar diagrams that depict the mean relative chemotaxis of CLL cells after stimulation with anti-IgM (▩) or after stimulation with anti-IgM in the presence of R406 (■), compared with unstimulated CLL cells (controls, 100%). Displayed is the mean (± SEM, n = 10) chemotaxis toward CXCL12 and CXCL13, as indicated above the bars, for each of these conditions. R406 significantly inhibited the chemotaxis of CLL cells toward both CXCL12 and CXCL13 to levels that were even lower than the chemotaxis of control cells. The asterisks indicate a significant reduction of chemotaxis with P < .05. (B) Coculture of CLL cells with MSC results in the spontaneous migration of CLL cells beneath the MSC (pseudoemperipolesis). We investigated whether treatment with anti-IgM could increase migration of CLL cells beneath marrow stromal cells, and we also evaluated the effect of R406 on pseudoemperipolesis. As displayed, BCR triggering with anti-IgM significantly increased pseudoemperipolesis to 130.4% ± 8.3% of controls, and preincubation with R406 decreased the percentage of migrated cells to 88.8% ± 20.3% of control (mean ± SEM, n = 6). *P < .05.