Schematic overview of the potential therapeutic benefits of a novel epigenetic treatment strategy for T-ALL, as described by Han et al. Next to the current standard of care (chemotherapy), several targeted therapies have emerged. These include immunotherapies, the BCL-2 inhibitor venetoclax, and tyrosine kinase inhibitors (TKI). The promising new approach involves direct inhibition of the histone modifier WDR5 using OICR-9429. Adding indirect WDR5 inhibition by targeting the casein kinase 2 (CK2)-IKAROS axis through the cell cycle repressor CX-4945 resulted in remarkable synergistic activity.