Figure 3
From: Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors
DIMATE shows potent activity against primary AML cells transplanted in NOG mice. (a) Experimental scheme and gaiting strategy in flow cytometry for hCD45+ and mCD45+ cells monitoring in blood, spleen and bone marrow for study of the antileukemic activity of DIMATE in immunodeficient mice engrafted with primary human AML cells. Mice were randomized and treatment with DIMATE (14, 28 mg/kg) and vehicle started for 4 weeks. Weekly monitoring of hCD45+ and mCD45+ circulating cells were performed during the treatment. After treatment, mice were killed and bone marrow and spleen were harvested. CD45+ have been sorted and monitored in spleen and bone marrow. Spleen weighing was performed. (b) Human CD45+ cells (hCD45+) count in peripheral blood during the treatment with vehicle or DIMATE. (c) Mouse CD45+ cells (mCD45+) count in peripheral blood during the treatment with vehicle or DIMATE. (d) Absolute human AML cells in the peripheral blood of NOG mice engrafted with AML cells before and after treatment with vehicle and different concentrations of DIMATE after mice euthanasia. (e) Counts of human CD45 cells in spleen in mice engrafted with AML cells after treatment with vehicle and different concentrations of DIMATE. (f) Counts of human CD45 cells in bone marrow in mice engrafted with AML cells after treatment with vehicle and different concentrations of DIMATE. (g) Spleen weight of mice transplanted with human AML cells treated with vehicle or DIMATE. In panels (d–f) each symbol denotes a single animal (n=3–6 per group). ** Mean P<0.001 and * mean P<0.05.
