TCF4 DNA copy number gains drive immunoglobulin expression and can be targeted by BET degraders. (A) DNA copy number gains of chromosome 18q increase the expression of the TCF4 (E2-2) transcription factor, which drives increased expression of IgM. (B) The TCF4 gene is regulated by BRD4. BET protein degraders such as ARV-771 eliminate BRD4 protein and reduce the expression of TCF4 and its target genes, including IgM and MYC.