Fig. 1. CRL4^CRBN E3-ubiquitin ligase complex regulation and features of the CRBN mutation identified.

A Diagram outlining the regulation of the CRL4^CRBN E3-ubiquitin ligase complex, indicating the “CRBN/IMiD” genes analysed in this study. B The clonal evolution pathway from presentation to relapse determined by the Cancer Clonal Fraction for all mutations in the patient sample with a CRBN mutation detected by whole-exome sequencing using 2D Kernal Density Estimate plot of the CCF. This suggests a branching evolutionary pattern leading to relapse with distinct clusters of mutations seen at presentation only, relapse only, and at both time points. C Structure of Lenalidomide-bound human CRBN/DDB1 complex, highlighting the participation of Cys326 in a Zinc finger motif within the Thalidomide Binding Domain (TBD) of CRBN. Figure generated with Pymol using coordinates from PDB 4TZ4 (10.1038/nsmb.2874).