Extended Data Fig. 10: WM-1119 is effective in inhibiting tumour progression.
From: Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
a, Tumour development monitored by luciferase activity and bioluminescence imaging. Lateral images of mice treated four times per day with either vehicle or WM-1119 between day 7 and day 14 after injection with tumour cells. Baseline tumour burden is shown at higher sensitivity setting for day 3 (before treatment) in Fig. 4. Here, images at days 7, 10, 12 and 14 after tumour cell transplant are shown on the same, less-sensitive scale. Mice are imaged in the same order. Red boxes indicate the area used for quantification. b, Mouse body weights are not affected by treatment three or four times per day. c, Concentration of WM-1119 in peripheral blood and spleen 6 h after the final injection (four times per day; n = 6 mice per treatment group). d, Flow-cytometry analysis of total spleen cells from vehicle- or WM-1119-treated groups (four times per day; analysis of spleens assayed in a to identify tumour cells independently of luciferase expression). The lymphoma cell line EMRK1184 has a cell surface phenotype of CD19+IgM−IgD−. Flow cytometry was used to quantify the CD19+IgD− population; this can be distinguished from normal splenic B cell populations, which are CD19+IgD+. e, Intracellular flow-cytometry analysis of H3K9ac in tumour cells. Left, the histogram shows H3K9ac levels in the remaining tumour cells (CD19+IgM−) in spleens of the WM-1119-treated mice (red profile) compared to the vehicle-treated mice (blue profile). The shift in the red (WM-1119-treated) profile compared to the blue (vehicle-treated) profile indicates a reduction in signal. Right, the median fluorescence intensity (mean ± s.e.m) is shown in the bar graph. f, Peripheral blood analysis of vehicle- or WM-1119-treated mice. The cohort of mice that was treated three times per day is compared to the cohort that was treated four times per day. Images representative of n = 9 mice per treatment group in the four-times-per-day treatment regime (a). n = 3 mice per treatment group (b, d–f) and n = 6 mice per treatment group in (c). Data are mean ± s.e.m. and were analysed by one-way ANOVA with treatment as the independent factor followed by Bonferroni post hoc test (b), or two sided t-test (c, d, f) or one-sided t-test (e).
