Degradation of BET proteins with the BET proteolysis-targeting chimera ARV-825 resulted in downregulation of both CXCR4 and CD44 in AML cells, and as a result impairment of CXCL12-directed migration, increased oxidative stress, and downregulation of gene signatures associated with “stemness” and Wnt/β-catenin and Myc pathways. Here, DNER is linked to acute myeloid leukemia.