| Popis: |
Notch signaling pathway consists of three parts: Notch receptor, Notch ligand and intracellular effector. Notch is a family of transmembrane proteins that function both as cell surface receptors and transcription regulators. As the first human gene of this family, Notch1 was discovered in 1991 through the analysis of the chromosomal translocation t(7;9) (q34;q34.3) observed in patients with T-cell acute lymphoblastic leukemia (T-ALL). Since then Notch signaling has been implicated in multiple processes that govern normal morphogenesis, differentiation, cell proliferation and apoptosis. At the same time a role of Notch in the pathogenesis of hematologic and solid malignancies has become apparent. The identification of activating mutations in Notch1 were discovered in over 50% of T-ALL patients. However, whether the mutation in Notch1 is an early event or an secondary event is still unknown. It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive. This review focuses on the recent findings regarding the Notch signaling during the development and progression of different kinds of hematologic malignancies, the types of mutations in Notch1 in T-ALL and the relationship between Notch signaling pathway and other signaling pathways.In addition, the clinical prospects of Notch inhibitors also are discussed. |
