Figure 6.

Interfering with MYC:MAX dimerization as a therapeutic strategy. Dose response curves for MYC:MAX dimerization inhibitor MYCi361 in Gata1s-FLC cells (A, left) and in ML-DS blasts derived from 3 patients (B, left) 24 hours after treatment in vitro. Corresponding IC₅₀ values are depicted below the graphs. Bar graphs showing the percentage of annexin V⁺ cells after treatment with the indicated doses of MYCi361 compared with the dimethyl sulfoxide control in Gata1s-FLCs (A, right) and in ML-DS blasts (B, right); data represented as mean ± SD (n = 3, 1-way ANOVA). (C) Experimental setup for evaluating MAX dependence in ML-DS and AMKL cells in vivo. ML-DS or AMKL blasts derived from 2 patients were transduced with short hairpin MAX (shMAX) (GFP⁺) or short hairpin control (shCtrl) (GFP⁺) and mixed 1:1 with shCtrl-transduced blasts (dTomato⁺), before transplantation into sublethally irradiated recipient mice. (D) Ratio of GFP⁺ to dTomato⁺ cells in the bone marrow of mice euthanized 4 to 8 weeks after transplantation (n = 5, Kruskal-Wallis test).