Understanding whether the H3K4 trimethylation activity of KMT2B is disturbed in KMT2A-rearranged leukemia, and particularly in context with KMT2A::AFF1 and KMT2A::MLLT3 fusion genes, represents an intriguing next chapter in illuminating the pathobiology of KMT2A-rearranged leukemia. This evidence concerns the gene KMT2B and leukemia.