Figure 5.

Ablation of AE function in leukaemic mice. Each square and dot represents one mouse. * p < 0.05; ** p < 0.01; *** p < 0.001; ns, not significant.

1. Experimental design.

2. Mean WBC counts ± SD from controls (white squares), continuously DOX-exposed (+DOX) mice, animals that had been shifted to a DOX-free diet with disease progression and animals with signs of recovery (−DOX). Two-tailed unpaired t-test analysis demonstrated significant differences in WBC counts between controls and continuously DOX-exposed mice (p = 0.0023), controls and animals that had been shifted to a DOX-free diet with disease progression (p = 0.0339) and controls and animals with signs of recovery (p = 0.0181). No statistically significant differences in WBC counts were detected between continuously DOX-exposed mice and recovered animals (p = 0.0639) and also between animals that had been shifted to a DOX-free diet with disease progression and recovered animals (p = 0.2059).

3. The upper panel shows representative peripheral blood films from a mouse that was permanently exposed to DOX (+DOX) or shifted to a DOX-free diet and progressing with leukaemia (−DOX). The two images at the bottom show peripheral blood films from the same mouse before (+DOX, left image) and 16 weeks after the animal had been shifted to a DOX-free diet (−DOX, right image).

4. Individual spleen weight of control mice (white squares) and animals that were either continuously DOX-exposed (+DOX, red dots), shifted to a DOX-free diet and progressing with leukaemia (−DOX, orange dots) or shifted to a DOX-free diet and showing signs of recovery (−DOX, blue dots). Two-tailed unpaired t-test analysis demonstrated significant differences in spleen weight between controls and continuously DOX-exposed mice (p = 0.0049), controls and animals that had been shifted to a DOX-free diet with disease progression (p = 0.0001), controls and animals with signs of recovery (p = 0.03) and animals that had been shifted to a DOX-free diet with disease progression and recovered animals (p = 0.0086). No statistically significant difference in spleen weight between continuously DOX-exposed mice and recovered animals (p = 0.2051) was detected.

5. Bone marrow (BM) sections through the spinal cord of a control mouse, a mouse continuously exposed to DOX (+DOX), an animal shifted to a DOX-free diet with progressing leukaemia (−DOX, orange) and a mouse shifted to a DOX-free diet showing signs of recovery (−DOX, blue). Black arrowheads indicate immature myelocytes/blast-like cells. Note the increase of big blast-like cells in the two sections in the middle and the decrease of these cells in the section on the right (−DOX, blue).

6. Flow cytometric analysis of immature (CD11b⁺Gr1^low) and more mature (CD11b⁺Gr1^high) cells within the BM population of granulocytes for control mice (white squares), animals continuously receiving DOX (+DOX, red dots), animals that had been shifted to a DOX-free diet presenting signs of progressing leukaemia (−DOX, orange dots) and mice that had been shifted to a DOX-free diet presenting signs of recovery (−DOX, blue dots).