Figure 7.
Anti-leukemia activity of α-FLT3-A192 in FLT3-ITD murine model. Fig. A-F: 2.5 × 106 cells MOLM-13 cells/mouse were engrafted in NSG mice. Mice were treated with 200 μL of 220 μM of A192 (n = 8) or α-FLT3-A192 (n = 8) on day 7, 10, 13 and 16 post engraftment and euthanized on day 17. 100 mg/kg Midostaurin (N = 3) on day 7–11 post leukemia engraftments. A) Images of mice spleens show decreased in spleen size in mice treated with α-FLT3-A192 compared with A192 treated mice. Enlargement of spleen is consistent with progression of this AML model in A192 control mice. B) Spleen’s weights were measured, and spleens of mice treated with α-FLT3-A192 weighed significantly less compared with the A192 treated mice (0.48 vs. 126 mg, p = .03). C-D) Leukemia engraftment was measured using human CD45 (huCD45) antibody by flow cytometry in the peripheral blood (%huCD45- α-FLT3-A192: 17.5 vs. A192: 43.44, p =0 .01) and (%huCD45- midostaurin: 13.73 vs. A192: 43.44, p = .03) E-F) Similarly, CD45 engraftment was reduced by α-FLT3-A192 treatment in the bone marrow (%huCD45- α-FLT3-A192: 10.2 vs. A192: 26.1%, p < .0001) and (%huCD45- midostaurin: 11.59 vs. A192: 26.1%, p = .0003). There was no difference in the engraftment of mice treated with midostaurin or α-FLT3-A192. G) 2.5 × 106 MOLM-13 cells/mouse were engrafted in NSG mice and treated with 200 μL of 220 μM A192 (n = 7) or α-FLT3-A192 on day 7, 10, 13 and 16 post engraftment and survival was recorded. Kaplan Meier survival analysis showed that mice in the α-FLT3-A192 treatment group survived significantly longer than mice in the A192 group (median survival: 36 vs. 30 days, p = .0015).