Overcoming apoptosis resistance in high risk acute lymphoblastic leukemia by SMAC mimetics in a preclinical all xenograft model

* equal contribution Defects in cell death signaling e.g. overexpression of “Inhibitor of Apoptosis” (IAP) proteins might be one reason for treatment failure of acute leukemia. Therefore, IAP antagonists, so called SMAC mimetics (SMs), provide a promising novel treatment strategy for ALL. We investigated the effects of SMs on 42 primary ALL samples. Intriguingly, 70% of all patient-derived leukemias showed cell death induction after SM-treatment in a TNFα-dependent manner. Interestingly, also high-risk ALL samples with constitutive deficient apoptosis signaling showed increased cell death upon SM-treatment and a…