SM and HDACi cooperate to delay leukemia progression in vivo. (A) Schematic representation of experimental setup. (B) Representative examples of leukemia progression dynamics during treatment of 4 PDXs. Shaded in blue is the treatment window. (C) Time elapse (in days) to reach ALL progression of 20% in peripheral blood, calculated between treated mouse and the respective control (vehicle) for each PDX (vehicle – treatment). A log-rank (Mantel-Cox) test revealing significant differences in progression for mice treated with the single agents vs combinatorial treatment. (D) ALL-progression difference, indicating the difference in leukemia percent (in peripheral blood) calculated between control mouse and treated mouse (vehicle – treatment) at the end point of control mice, relative to each PDX. Same treatment conditions are plotted together. The Wilcoxon matched-pairs signed rank test revealing significant differences in progression for mice treated with the single agents vs combinatorial treatment. Median is depicted. Leukemia percent is calculated based on hCD19⁺ cells over the total lymphocyte population (hCD19⁺ + mCD45⁺). Gray, vehicle; red, birinapant; green, Mo; blue, combination. SM, birinapant 15 mg/kg; Mo, 25 mg/kg; SM + Mo, birinapant 15 mg/kg + Mo 25 mg/kg. Eight PDXs are included. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗∗P ≤ .0001. (E) Graphical representation of the proposed mechanism of transcriptional regulation of SM-induced cell death in ALL.