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

Abstract

Home Notch Regulation of the Immune System Chapter Notch1 and IL-7 Receptor Signalling in Early T-cell Development and Leukaemia Download book PDF Download book EPUB Notch1 and IL-7 Receptor Signalling in Early T-cell Development and Leukaemia Sara González-García, Marina García-Peydró, Juan Alcain & María L. Toribio Chapter First Online: 01 January 2012 3330 Accesses

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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.