Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Line, Tumor
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Cell Proliferation
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Disease Models, Animal
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Humans
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Phenotype
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Receptor, Notch1 / genetics
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Receptor, Notch1 / immunology*
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Receptors, Antigen, T-Cell / immunology*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Notch1 protein, mouse
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Receptor, Notch1
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Receptors, Antigen, T-Cell