Notch and T cell malignancy

Notch signaling is required for normal T cell development. However, Notch expression must be precisely regulated as constitutive Notch signaling leads to T cell lymphomas. Recent evidence has provided insights into potential mechanisms of Notch-mediated lymphomagenesis and its relationship to T cell development. The evidence suggests that Notch likely interacts with several important cellular pathways and can cooperate with other oncogenes during lymphomagenesis. In particular, Notch appears to modulate pre-TCR signaling, inhibit the E2A pathway, and in murine leukemia models, frequently cooperates with Myc, E2A-PBX and dominant negative Ikaros dysregulation. This review will present current knowledge in these areas and explore theories on Notch-mediated T cell lymphomagenesis.