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. Author manuscript; available in PMC: 2023 May 1.
Published in final edited form as: Leukemia. 2022 Oct 11;36(11):2621–2633. doi: 10.1038/s41375-022-01719-6

Figure 5. Autophagy inhibition reduces repopulating capacity of FLT3-ITD AML stem cells in a genetic mouse model.

Figure 5.

A: Experimental design: FLT3-ITD AML mice were treated for 2 weeks with vehicle, Lys05, AC220 or the combination of Lys05 and AC220, as described for Fig4A, and 2×106 BM cells (CD45.2+) obtained from treated mice were injected into irradiated (400cGy×2) recipient CD45.1 mice via tail vein together with 2×106 BM cells from wildtype CD45.1 mice (n=6-8). B: Donor myeloid chimerism from peripheral blood were monitored every 4 weeks. The total number of donor GMP and ST-HSC per 2 femurs and 2 tibiae (4 bones) are shown. C: LSK cells isolated from FLT3-ITDki /Mx1-Cre Tet2f/f leukemic BM were transduced with lentivirus vectors expressing ATG5-shRNA and GFP or ctrl-shRNA and GFP. Reduction in ATG5 protein levels in GFP+ cells was confirmed by Western blotting. Engrafted mice were treated with AC220 or vehicle for 2 weeks. Total number of GFP+ GMP and GFP+ ST-HSC in BM of recipient mice (2 femurs and 2 tibias) are shown (n=4-7). Significance values: *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; ns, not significant. Results represent mean ± SEM of multiple replicates.