Even though this mystery of differential sensitivity is still unresolved, the fact that chromatin reading by specific PZP and YEATS domains are critical for MLL-leukemogenesis opens up the exciting possibility of targeting MLL-rearranged leukemias using selective small-molecule inhibitors of these chromatin-reading modules that are likely to be developed in the near future. The gene discussed is KMT2A; the disease is leukemia.