Fig. 6: Pharmacological inhibition using the MOZ/MORF KAT inhibitor suppresses CALM-AF10-mediated leukemia in vivo.
From: MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins
a Leukemia burden before and after MOZ/MORF KAT inhibitor treatment. P31/FUJ human leukemia cells expressing LUC2Red were transplanted into sublethally irradiated SCID mice and intraperitoneally injected with WM1119 50 mg/kg (WM) or the 50% PEG400 vehicle control (VC) three times a day for 2 weeks, as shown in the top schema. Representative images of luciferase-mediated bioluminescence reflecting leukemia cell abundance are shown with scale bars. Quantification of leukemia burden by region-of-interest analysis of the IVIS images (mean ± SD of biological replicates, n = 10). Welch’s t-test (two-sided) was performed on the indicated two-group comparison. Survival of transplanted recipient mice with or without MOZ/MORF KAT inhibitor treatment (the duration of drug administration is indicated in the graph). A log-rank (Mantel–Cox) test was performed. b Proliferation of various AF10 fusion-ICs in the presence of MOZ/MORF KAT inhibitor (10 µM WM1119) was monitored for 21 days along with the vehicle control (DMSO). c Differentiation induced by MOZ/MORF KAT inhibitors. Flow cytometry analysis for the CD11b antigen was performed on the CALM-AF10-ICs treated with 10μM of WM1119 for 6 days. d Leukemia burden before and after MOZ/MORF KAT inhibitor treatment. Murine CALM-AF10 leukemia cells expressing LUC2Red were transplanted into sub-lethally irradiated syngeneic C57BL/6JJcl mice, treated with WM1119 as in a. Representative images of luciferase-mediated bioluminescence are shown as in a. Quantification of leukemia burden by region-of-interest analysis of the IVIS images (mean ± SD of biological replicates, n ≥ 7). Welch’s t-test (two-sided) was performed on the indicated two-group comparison. Survival of transplant recipient mice with or without MOZ/MORF KAT inhibitor treatment (the duration of drug administration is indicated in the graph). A log-rank (Mantel–Cox) test was performed. Source data are provided as a Source Data file.
