This leads to repression or inability to activate genes involved in CD40, BCR, TLR, and other immune pathways.103 Importantly, KMT2D mutation renders DLBCL cells resistant to CD40 signaling due to suppression of CD40‐responsive enhancers.103 Since KMT2D mutations result in reduction (but not total ablation) of H3K4 methyltransferase activity in B cells, it is reasonable to hypothesize that loss of enhancer activation due to KMT2D mutation is maintained and reinforced by histone demethylases, analogous to the case of CREBBP and HDAC3 on histone acetylation. This evidence concerns the gene CD40 and diffuse large B-cell lymphoma.