In acute lymphoblastic leukemia (ALL), we identified RIP1 as a critical regulator of the synergism of Smac mimetics and Cytarabine, which mediates the formation of a RIP1/caspase-8/FADD complex via an autocrine/paracrine loop of tumor necrosis factor-α (TNFα) and is necessary for activation of caspase-8 and -3, mitochondrial perturbations and apoptosis [16]. Here, FADD is linked to acute lymphoblastic leukemia.