Figure 6.
The pharmacological inhibition of LCK together with Dex treatment reduces T-ALL engraftment in GC-resistant PDX mice. (A) Outline of treatment with Dex and dasatinib alone and in combination, or control mice (vehicle). NSG mice (n = 6 per group) were treated intraperitoneally with Dex (5 mg/kg), by oral gavage with dasatinib (35 mg/kg), or by vehicle 18 days after IV injection of PD-TALL40 cells (5 × 106 cells/mouse). Compounds were subsequently administered daily for 3 weeks (blue arrows). Leukemia engraftment was tracked by serial blood drawings and flow cytometric analysis (green arrows). (B) Quantification of leukemia cells (CD7+) in the PB, BM, and spleen at sacrifice (day 36 from injection) by flow cytometry and human CD7 staining. Mann-Whitney t test. The average percentage of CD7+ cells in control mice was set to 100%. Results are presented as means ± SEM. (C) Outline of treatment, as described in panel A, 11 days after IV injection of PD-TALL18 cells (5 × 106 cells/mouse). Compounds were subsequently administered daily for 2 weeks (blue arrows). Leukemia engraftment was tracked by serial blood drawings and flow cytometric analysis (green arrows). (D) Quantification of leukemia cells (CD7+) in the PB, BM, and spleen at sacrifice (day 24 from injection) by flow cytometry and human CD7 staining. Mann-Whitney t test. The average percentage of CD7+ cells in control mice was set to 100%. Results are presented as means ± SEM. CIs are 0.6 (PB), 0.14 (BM), and 0.34 (spleen). *P < .05; **P < .01.