HES1 and acute lymphoblastic leukemia: The high apoptotic levels induced by curcumin in NT1-M CLL cells were also associated with a drastic reduction of NOTCH1 signaling, as shown by the decreased levels of the active NICD and its downstream targets HES1 and DTX1. In line with these findings, experiments with a derivative of the SERCA inhibitor thapsigargin demonstrated that T-ALL cells harboring NOTCH1 mutation showed a marked reduction in the NOTCH1 signaling pathway (50).