Depletion of SP1, p300, or HDAC2 alters sensitivity toward SM in different PDXs. (A) Immunoblot showing depletion of p300 upon treatment for 6 hours with various concentrations of dCBP1 or DMSO in 2 PDXs. GAPDH is used as a loading control (left). Dot plot showing normalized AUC upon SM treatment in 10 SM-sensitive BCP-ALL with or without pretreatment with dCBP1 for 6 hours (right). The Wilcoxon matched-pairs signed rank test revealing significant differences in normalized AUC. PDXs included PID0036, PID0556, PID0872, PID0083, PID0788, PID0874, PID0117, PID0852, PID0859, and PID0858. (B) Box plot showing SM normalized AUC from 7 BCP-ALL PDXs treated with indicated p300 inhibitors (A-485, 0.1-10 μM; INB, 0.01-1 μM; concentration ranges were selected based on different potencies of the compounds). The Wilcoxon matched-pairs signed rank test detecting differences in the normalized AUC upon SM treatment after pretreatment with different p300 inhibitors compared with SM alone (gray∗) or compared with increasing concentrations of the same inhibitors (black∗). Median is displayed for each condition. PDXs included PID0556, PID0083, PID0874, PID0117, PID0852, PID0859, and PID0858. (C) Bar plot depicting the ratio of RPF657⁺ population (construct-containing population) calculated on human CD19⁺ (hCD19⁺) population in spleens of mice treated with SM over spleens of mice treated with vehicle. HDAC2, population containing LC.RFP657.HDAC2 construct; shuttle, population containing LC.RFP657.shuttle construct (used as control); SP1, population containing LC.RFP657.SP1 construct. No difference, y = 1; enrichment, y > 1; depletion, y < 1. Dot plot depicts hCD19⁺ cells percent over the total lymphocyte population (hCD19⁺ + mCD45⁺) in mice’s spleens at the end of treatment. Multiple comparison 2-way analysis of variance (ANOVA) analysis showing significant difference in ALL population in SM-treated HDAC2-depleted PID0117 spleen compared with the shuttle counterpart. ns, P > .05; ∗P ≤ .05; ∗∗P ≤ .01 ∗∗∗∗P ≤ .0001.