Figure 3
Figure 3. Role of the SDF-1/CXCR4 axis in adult ALL migration and engraftment. (A) Representative histograms of CXCR4 receptor expression in t(4;11), non-t(4;11) pre-B ALL, and CD34+ MPBSCs. Illustrations correspond to cases 3, 7, and 1, respectively, in Table 4. CXCR4 at the cell surface (gray line), intracellularly (dotted line), and isotype control (black line) are shown. (B) Transwell migration toward a gradient of SDF-1 [0-1000 ng/mL in non-t(4;11), n = 7; t(4;11), n = 3; and CD34+ MPBSCs, n = 3]. Results show mean ± SEM of fold change in absolute numbers of migrating cells per microliter normalized to spontaneous migration without SDF-1. Results are from 3 to 5 independent experiments from each group.*P < .05 compared with respective control; ●P < .05; ▲P = .07. (C) Non-t(4;11) pre-B ALL cells from 2 patients were pretreated with vehicle or AMD1300 and then assayed for transwell migration toward SDF-1 (125 ng/mL). The number of migrating cells was determined after 4 hours in transwell culture. Data points show duplicates for each sample together with mean ± SEM. **P = .003 compared with vehicle. (D) Pre-B ALL cells from a single patient were treated with isotype control or anti-CXCR4 blocking antibody. Results show (lower) the percentage of CD45+/CD19+ cells in BM +14 days after injection in representative mice and (upper) the absolute number of leukemia cells in harvested BM 4 weeks following injection in individual recipients. Four mice were used for each treatment. *P = .03 compared with control.

Role of the SDF-1/CXCR4 axis in adult ALL migration and engraftment. (A) Representative histograms of CXCR4 receptor expression in t(4;11), non-t(4;11) pre-B ALL, and CD34+ MPBSCs. Illustrations correspond to cases 3, 7, and 1, respectively, in Table 4. CXCR4 at the cell surface (gray line), intracellularly (dotted line), and isotype control (black line) are shown. (B) Transwell migration toward a gradient of SDF-1 [0-1000 ng/mL in non-t(4;11), n = 7; t(4;11), n = 3; and CD34+ MPBSCs, n = 3]. Results show mean ± SEM of fold change in absolute numbers of migrating cells per microliter normalized to spontaneous migration without SDF-1. Results are from 3 to 5 independent experiments from each group.*P < .05 compared with respective control; ●P < .05; ▲P = .07. (C) Non-t(4;11) pre-B ALL cells from 2 patients were pretreated with vehicle or AMD1300 and then assayed for transwell migration toward SDF-1 (125 ng/mL). The number of migrating cells was determined after 4 hours in transwell culture. Data points show duplicates for each sample together with mean ± SEM. **P = .003 compared with vehicle. (D) Pre-B ALL cells from a single patient were treated with isotype control or anti-CXCR4 blocking antibody. Results show (lower) the percentage of CD45+/CD19+ cells in BM +14 days after injection in representative mice and (upper) the absolute number of leukemia cells in harvested BM 4 weeks following injection in individual recipients. Four mice were used for each treatment. *P = .03 compared with control.

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