Figure 1.
Inducible models of AF10 FP AML. (A) Schematic representation of the BM transplantation model (see “Methods” for detailed description). (B) Number of blast-like and differentiated colonies in 2 serial replatings in AF10-fusion expressing dimethyl sulfoxide (DMSO)-treated cells (On) and Dox-treated AF10-fusion (Off) preleukemia cells are shown. *P < .05; **P < .005; ***P < .01. P values were calculated using the Student t test. iCALM-AF10 colonies are show on the left panel and iMLL-AF10 on the right. Representative images of colonies from indicated AF10 fusion-transformed BM cells with DMSO (AF10 fusion-On) compared with Dox-treated (AF10 fusion-Off) are shown below (original magnification ×10). Also shown are Wright-Giemsa–stained cytospins from the different indicated conditions (original magnification ×40). (C) Kaplan-Meier survival curves for secondary mice with the iCALM-AF10 fusion AMLs (CALM-AF10-On) administered normal chow compared with (iCALM-AF10-Off) mice administered Dox chow are shown in the left panel and for iMLL-AF10 mice is shown on the right panel. Number of mice in each group and P value of differences between 2 groups (log-rank Mantel-Cox test) are shown. (D) Number of genes significantly downregulated (P < .05) when the respective fusion oncoproteins were switched-off using Dox within 48 hours are shown, with overlaps displayed in the Venn diagram. (E) Heatmaps for the 25 genes downregulated by all the 3 indicated AML-associated FPs are shown with gene names. Genes previously implicated in leukemia stem cell biology are marked in red.