The expression ofRIP3-KD induced p65/RelA nuclear factor-κB(NF-κB) subunit caspase-dependent cleavage, and anon-cleavable p65/RelA D361E mutant rescued these cells from apoptosis.p65/RelA cleavage appears to be at least partially mediated by caspase-6.These data indicate that RIP3 silencing in leukemia cells results in suppressionof the complex regulation of the apoptosis/necroptosis switch andNF-κB activity. The gene discussed is CASP6; the disease is leukemia.