Furthermore, CREBBP mutations are present at higher frequency in R/R DLBCL cohorts, compared to primary DLBCL [34,52] Notably, MLL2 and MLL3 act as coactivators at enhancers and prime enhancers for gene activation through the recruitment of CBP and p300, indicating functional interaction between these two different families of histone modifiers [137]. This evidence concerns the gene KMT2C and diffuse large B-cell lymphoma.