Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies.
Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context- and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T-cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling. Remarkably, it appears that the selective pressure for Notch mutations is virtually unique among cancers to T-LL, presumably reflecting a special context-dependent role for Notch in normal T-cell progenitors. Nevertheless, there are some recent reports suggesting that Notch signalling has subtle, yet important roles in other forms of haematological malignancy as well. Here, we review the role of Notch signalling in various blood cancers, focusing on T-LL with an eye towards targeted therapeutics.
Aster
Jon C
JC
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. jaster@rics.bwh.harvard.edu
Blacklow
Stephen C
SC
Pear
Warren S
WS
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D051881:Receptor, Notch1 / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D051880:Receptors, Notch