We first inhibited the NOTCH pathway by incubating our cell lines with 1μM of compound E, an inhibitor of γ-secretase (Figure 4A). Among the 2 cell lines that harbored NOTCH1 mutations, a striking effect on proliferation was observed in Rec-1 (mean percentage of EdU-incorporating cells decreasing from 47.2% to 18.9%, P < .001), whereas Mino showed only a minimal decrease in proliferation (from 53.9% to 50.4%, P = .002). Indeed, inhibition of the NOTCH pathway by either compound E or a dominant-negative Mastermind-like 1 construct resulted in reduced proliferation and/or increased apoptosis in 2 of 10 MCL cell lines.