Using this model system, we showed that both pharmacological inhibition and genetic depletion of CASP-8 increase the level of full length CRBN, enhance the degradation of IKZF1 and IKZF3, and then suppress the proliferation of myeloma cells when treated with Len, which is consistent with the previous studies that CRBN protein levels control the sensitivity to IMiDs (Zhu et al., 2011; Liu et al., 2019). Here, IKZF1 is linked to plasma cell myeloma.