T cell acute lymphoblastic leukemia: NOTCHing the way toward a better treatment outcome.

Gamma-secretase inhibitors block the activation of NOTCH1 but have limited activity against T cell acute lymphoblastic leukemia (T-ALL) and cause severe gastrointestinal toxicity. In a recent study, Real et al. show that a potent gamma-secretase inhibitor potentiates the cytotoxicity of dexamethasone against glucocorticoid-resistant T-ALL cells, while dexamethasone abrogates the gastrointestinal toxicity induced by the gamma-secretase inhibitor.