The identification of frequent activating NOTCH1 mutations in T-ALL has attracted significant interest in targeting the NOTCH1 signaling pathway for treatment.11 Several strategies have been undertaken to block NOTCH1 pathway signal transduction, including preventing ligand-triggered activation or NOTCH1 autoactivation by using monoclonal antibodies such as OMP-52M51, which binds to the negative regulatory domain of NOTCH1.43 In addition, γ-secretase inhibitors (GSIs) have been utilized to inhibit the γ-secretase-induced cleavage and release of the intracellular domain of NOTCH1 (ICN1). Here, NOTCH1 is linked to acute lymphoblastic leukemia.