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Notch1 and IL-7 Receptor Signalling in Early T-cell Development and Leukaemia

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Notch Regulation of the Immune System

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 360))

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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Acknowledgments

This work was supported by grants from Plan Nacional (SAF2010-15106), Subprograma de Fomento de la Cooperación Científica Internacional (PLE-2009-0110), Fundación Sandra Ibarra and Instituto de Salud Carlos III (RD06/0014/1012) and by an institutional grant from the Fundación Ramón Areces. S.G–G was supported by Ministerio de Ciencia e Innovación (MICINN) (FPI program). The authors declare no conflicting financial interests.

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  1. Centro de Biología Molecular “Severo Ochoa” Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049, Madrid, Spain

    Sara González-García, Marina García-Peydró & Juan Alcain

  2. Centro de Biología Molecular “Severo Ochoa”, Universidad Autónoma de Madrid, C/Nicolás Cabrera1, 28049, Madrid, Spain

    María L. Toribio

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  1. Sara González-García
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Correspondence to María L. Toribio .

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    Freddy Radtke

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González-García, S., García-Peydró, M., Alcain, J., Toribio, M.L. (2012). Notch1 and IL-7 Receptor Signalling in Early T-cell Development and Leukaemia. In: Radtke, F. (eds) Notch Regulation of the Immune System. Current Topics in Microbiology and Immunology, vol 360. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_231

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