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.
Zweidler-McKay
Patrick A
PA
Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Pear
Warren S
WS
D000818:Animals; D006801:Humans; D016399:Lymphoma, T-Cell / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D051880:Receptors, Notch; D015398:Signal Transduction
D008565:Membrane Proteins; D051880:Receptors, Notch