Fig. 2

In vivo activity of M3258 in ALL models. (a) NSG mice bearing orthotopic tumors of luciferase expressing SEM cells were dosed daily by oral gavage for four weeks with either M3258 (10 mg/kg) or vehicle control, and tumor growth was assessed by bioluminescent imaging. Statistical analysis of growth data was conducted by a t-test; n = 6 (control); n = 7 (M3258-treated). Survival data here and in all subsequent panels was analyzed by the log-rank test. (b) NRG mice bearing the same tumors were treated as indicated and tumor growth was assessed by bioluminescent imaging. Left and right graphs present results of the same experiment. Slopes of log₁₀(tumor growth) curves were estimated using linear mixed model with a random intercept for each mouse (Supplementary Table S2), and growth rates were compared using Bonferoni correction; n = 8. (c) NRG mice engrafted with MLL-86 cells were treated with Btz, M3258, and the same combination chemotherapy at the same schedule and doses as in panel b; n = 8. Left panel, survival of animals. Right panel, contribution of β5i to the chymotrypsin-like activity of proteasomes in 85–95% pure MLL-86 cells isolated from animals’ spleens.