EF7: Impact of BKM120/Ketogenic combination on a syngeneic model of AML.

(A) IVIS images of AML burden (as reported by DS-red) in these mice from these studies over time. The group of BKM plus keto diet were pre-treated with keto diet. N = 7 mice per arm. (B) Survival curves of mice from A with additional mice to evaluate pre-treatment vs co-treatment with the ketogenic diet in the syngeneic model of AML treated with BKM120 alone or in combination with a ketogenic diet. Individual lines are shown for initiation of ketogenic diet before (pre) or at the same time as the initiation of BKM120 treatment (Co), both demonstrate that BKM120 efficacy is significantly enhanced by the addition of the ketogenic diet (p = 0.0142 and 0.0316 by Gehan-Breslow Wilcoxon test for pre and co compared to BKM alone respectively). * denote mice that were sacrificed due to paralysis resulting from AML infiltrating the CNS rather than deaths typically seen in these mice due to tumor burden. Of note the mice in the BKM + Ketogenic diet group were frequently sacrificed due to paralysis which was not frequently a cause of mortality in the other treatment groups. N = 6,6,5,7,5,7 mice per arm for Vehicle, Pre-Ketogenic diet, Co-Ketogenic Diet, BKM120, Co-ketogenic Diet + BKM120, and Pre-Ketogenic diet + BKM120 arms respectively. (C) Disease burden of AML as measured by percent DS-red positive AML cells in bone marrow and (D) spleen weight across the treatment groups (pre-treatment with keto diet). Data are mean ± s.d. N = 5,4,4,4 mice per arm for Vehicle, Pre-Ketogenic diet, BKM120, and Pre-Ketogenic diet + BKM120 arms respectively (E) Measurement of AML burden in mice that were pretreated with BKM120 and/or a ketogenic diet to demonstrate that the effects observed in the AML studies are not the result of implantation issues related to the pretreatment. Data are mean ± s.d. N = 4,4,4,5 mice per arm for Vehicle, Pre-Ketogenic diet, BKM120, and Pre-Ketogenic diet + BKM120 arms respectively. (F) Images of mice treated as indicated with BKM120 and ketogenic diet where the diet and BKM120 therapy were initiated on the same day (co-treatment). N = 5 mice per arm.