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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 8. Autophagy inhibition differentially modulates p53 activity in TKI-treated FLT3-ITD AML progenitor and stem cells.

Figure 8.

A: Enrichment plot for combination of Lys05 and AC220 comapred with AC220 treatment for GMP cells (left). The expression of p53 target genes, p21, Bax, Noxa and Puma, measured by Q-RT-PCR in GMP cells treated with the Lys05 or/and AC220 for 2 weeks in vivo (n=3-5) (middle). Expression of p53 target genes, p21, BAX, NOXA and PUMA, in FLT3-ITD AML CD34+ cells after treatment with Lys05 or/and AC220 for 48 hours(n=4) (right). B: Enrichment plot for combination of Lys05 and AC220 comapred with AC220 treatment for LSK cells (left). The expression of p53 target genes, p21, Bax, Noxa and Puma, measured by Q-RT-PCR in LSK cells treated with the Lys05 or/and AC220 for 2 weeks in vivo (n=3-5) (right). C: LSK cells isolated from FLT3-ITDki /Mx1-Cre Tet2f/f leukemic BM were transduced with lentivirus vectors expressing P53-shRNA and GFP or ctrl-shRNA and GFP. Engrafted mice were treated with Lys05, AC220 or vehicle for 2 weeks. Reduction in P53 protein levels in GFP+ cells was confirmed by Western blotting. Total number of GFP+ myeloid cells and GFP+ ST-HSC in BM of recipient mice (2 femurs and 2 tibias) are shown (n=3-5). Significance values: *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; ns, not significant. Results represent mean ± SEM of multiple replicates.