CRBN and acute myeloid leukemia: For example, chronic treatment of acute myeloid leukemia (AML) MV4-11 cells with increasing concentrations of bromodomain and extra-terminal (BET) PROTACs recruiting the Von Hippel–Lindau (VHL) or cereblon (CRBN) E3 ligase led to the selection of resistant cells where the targeted protein had regained its original levels due to impairing mutations in the recruited ubiquitin ligase complexes [55].