Figure 6.

Targeting Vascular Permeability Cooperates with Chemotherapy to Improve AML Treatment

(A) Percentage of murine GFP⁺ MLL-AF9 #1 or tomato⁺ MLL-ENL #2 AML cells in the BM of secondary mice of depicted genotypes, treated with solvent or AraC; n = 3 or more replicates. Data are shown as mean ± SEM.

(B) Representative 3D reconstruction of calvarium BM of mice of depicted genotypes transplanted with murine MLL-AF9 #1 AML cells, treated with solvent or AraC. Scale bars represent 30 μm.

(C) Schematic of the experiment. Mice engrafted with human AML patients' samples were treated with AraC or solvent for 1 week, and with or without NOS inhibitors for 2 weeks.

(D) Activated NOS3 protein (measured by flow cytometry with an anti-phosphoSer1177 antibody) in CD31⁺ endothelial cells of the BM of mice transplanted with AML6 and AML9 patient-derived cells, treated as described in (C); n = 6. Data are shown as mean ± SEM.

(E) Hypoxia represented as HypoxiSense signal intensity/voxel in the calvaria BM of non-transplanted mice (ctrl) and mice transplanted with AML6 patient-derived samples, treated or not with AraC, as depicted. Ctrl UT, n = 13; ctrl AraC, n = 10; AML6 UT, n = 18; AML6 AraC, n = 20; AML6 A + N, n = 9; AML6 A + C, n = 9. Data are shown as whiskers minimum-to-maximum plots, the line inside the box representing the mean, the top and the bottom lines representing the 75% and 25% percentiles, respectively, and the lines above and below the box representing the SD.

(F) Percentage of human CD45⁺ engraftment in the BM of mice engrafted with patient-derived sample AML6 and treated as in (C); n = 3 per condition. Data are shown as mean ± SEM.

(G) Percentage of human CD45⁺ engraftment measured via BM aspirate in mice engrafted with AML 6 and treated as in (C). Data are shown as mean ± SEM.

ns, not significant; ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001. See also Figure S6.