NOTCH1 and acute lymphoblastic leukemia: As γ-secretase leads to the release of the intracellular domain of Notch1 (ICN1) and inhibition of γ-secretase is able to induce G0/G1 cell cycle arrest and inhibit T-ALL proliferation, plenty of GSIs were put into clinical trials, but failed because of gastrointestinal toxicity and limited anti-leukemia effects [33].