Both hits (IKZF1 and IKZF3) are established therapeutic targetsof lenalidomide in multiple myeloma.37 Theproteomic profiles generated across the seven molecules in MM1S (Figure 4D) show drug-dependentdegradation of the known neosubstrates including: transcription factorsIkaros (IKZF1) and Aiolos, (IKZF3), E3 ubiquitin-protein ligase ZFP91,and the translation termination proteins GSPT1 and GSPT2 (with vinculin,VCL, as loading control).37,39,52. Here, UBE2E3 is linked to AL amyloidosis.