Progress on Notch signaling in T-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common types of leukemia in children. With over 50 ％ of activating Notch1mutations in T-ALL,identification of activating Notch1mutations has brought interest toward targeting the Notch signaling pathway in this disease.Small-molecule γ-secretase inhibitors (GSI) can block a critical proteolytic step required for Notch1activation,but the clinical application of GSI has been hindered. Therefore, new therapeutic strategies aim to design of effective antiNotch1therapies in T-ALL are needed, including combination therapies with molecularly targeted drugs and glucocorticoids. This review put emphasis on the molecular basis of Notch1, the mechanisms of action of oncogenic Notch1and clinical significance of Notch 1mutations in T-ALL.