Chapter title |
Notch1 and IL-7 Receptor Signalling in Early T-cell Development and Leukaemia.
|
---|---|
Chapter number | 231 |
Book title |
Notch Regulation of the Immune System
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Published in |
Current topics in microbiology and immunology, June 2012
|
DOI | 10.1007/82_2012_231 |
Pubmed ID | |
Book ISBNs |
978-3-64-224293-9, 978-3-64-224294-6
|
Authors |
González-García S, García-Peydró M, Alcain J, Toribio ML, Sara González-García, Marina García-Peydró, Juan Alcain, María L. Toribio, González-García, Sara, García-Peydró, Marina, Alcain, Juan, Toribio, María L. |
Abstract |
Notch receptors are master regulators of many aspects of development and tissue renewal in metazoans. Notch1 activation is essential for T-cell specification of bone marrow-derived multipotent progenitors that seed the thymus, and for proliferation and further progression of early thymocytes along the T-cell lineage. Deregulated activation of Notch1 significantly contributes to the generation of T-cell acute lymphoblastic leukaemia (T-ALL). In addition to Notch1 signals, survival and proliferation signals provided by the IL-7 receptor (IL-7R) are also required during thymopoiesis. Our understanding of the molecular mechanisms controlling stage-specific survival and proliferation signals provided by Notch1 and IL-7R has recently been improved by the discovery that the IL-7R is a transcriptional target of Notch1. Thus, Notch1 controls T-cell development, in part by regulating the stage- and lineage-specific expression of IL-7R. The finding that induction of IL-7R expression downstream of Notch1 also occurs in T-ALL highlights the important contribution that deregulated IL-7R expression and function may have in this pathology. Confirming this notion, oncogenic IL7R gain-of-function mutations have recently been identified in childhood T-ALL. Here we discuss the fundamental role of Notch1 and IL-7R signalling pathways in physiological and pathological T-cell development in mice and men, highlighting their close molecular underpinnings. |
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Mendeley readers
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Demographic breakdown
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Student > Bachelor | 5 | 18% |
Student > Master | 5 | 18% |
Student > Ph. D. Student | 5 | 18% |
Other | 2 | 7% |
Researcher | 2 | 7% |
Other | 1 | 4% |
Unknown | 8 | 29% |
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Immunology and Microbiology | 2 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 1 | 4% |
Unknown | 9 | 32% |