Notch signaling: its roles and therapeutic potential in hematological malignancies
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Yisu Gu1, Massimo Masiero2,* and Alison H. Banham2,*
1 Department of Clinical Haematology, Oxford University Hospitals, Churchill Hospital, Oxford, UK
2 Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
* These authors have contributed equally to this work
Massimo Masiero, email:
Alison H. Banham, email:
Keywords: Notch, leukemia, lymphoma, hematology, therapy
Received: December 14, 2015 Accepted: February 11, 2016 Published: February 26, 2016
Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway.
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