Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling.
Overexpression of intracellular Notch plays an important role in the generation of human acute lymphoblastic T cell leukemia (T-ALL). In mouse models, it was shown that Notch-dependent T-ALL required pre-TCR signaling. Here we show that pre-TCR signaling is required to condition mice for Notch-dependent transformation but that it is not required to sustain malignant growth of T-ALL. In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2(-/-) mice by transient mimicking of pre-TCR signals.
Campese
Antonio F
AF
Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Garbe
Annette I
AI
Zhang
Fangrong
F
Grassi
Fabio
F
Screpanti
Isabella
I
von Boehmer
Harald
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D051881:Receptor, Notch1 / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell