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Objective Acute T-cell lymphoblastic leukemia (T-ALL) is a malignant disorder of thymocyte Progenitors,affecting both children and adults.The overall prognosis of T-ALL remains unsatisfied in comparison with B cell ALL and the outcome of T-ALL patients with primary resistant or relapsed leukemia is still poor.The frequent NOTCH 1 activating mutations and/or FBW7 loss-of-function mutations have vaulted dysregulated NOTCH signaling to the center of T-ALL pathogenesis.Yet the strategy of blocking the NOTCH signaling by γ-secretase inhibitors (GSIs) against T-ALL has not achieved substantial success in clinical treatments due to intolerable toxicity and/or insignificant efficacy.In order to circumvent the limitation of direct targeting of NOTCH1 that is currently used, we have sought alternative approaches for NOTCH1 inhibition, eg.targeting HSP90, and attempted to decipher the mechanism of action.