CASP8 and B-cell chronic lymphocytic leukemia: One possible explanation for the differential mode of cell death triggered by SHIP1 inhibition in CLL is the upregulated antiapoptotic machinery in CLL, one of the hallmarks of this disease: CLL cells express high ratios of c-FLIP(L) to caspase-8, and thereby prevent caspase-8 activation and apoptosis67, which can promote the induction of a necroptotic form of cell death68.