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

  • Sara González-García
  • Marina García-Peydró
  • Juan Alcain
  • María L. ToribioEmail author
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Thymus T-cell lineage Notch IL-7R lympho-myeloid progenitor leukaemia 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Sara González-García
    • 1
  • Marina García-Peydró
    • 1
  • Juan Alcain
    • 1
  • María L. Toribio
    • 2
    Email author
  1. 1.Centro de Biología Molecular “Severo Ochoa” Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridMadridSpain
  2. 2.Centro de Biología Molecular “Severo Ochoa”Universidad Autónoma de MadridMadridSpain

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