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PMID: 20967796 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies.

The Journal of pathology ·Vol. 223 ·No. 2 ·2011-01-00 ·Pages 262-73

Aster JC, Blacklow SC, Pear WS

Abstract

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.

MeSH Terms
Animals Biomarkers, Tumor/metabolism Hematologic Neoplasms/genetics,metabolism Humans Leukemia-Lymphoma, Adult T-Cell/genetics,metabolism Mice Mutation Oncogenes/genetics Receptor, Notch1/physiology Receptors, Notch/physiology Signal Transduction/physiology
Chemicals
Biomarkers, Tumor NOTCH1 protein, human Receptor, Notch1 Receptors, Notch
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Aster Jon C
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. jaster@rics.bwh.harvard.edu
Blacklow Stephen C
Pear Warren S
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Article Info
Journal
The Journal of pathology
Abbr.
J Pathol
ISSN
1096-9896
DOI
10.1002/path.2789
Email
jaster@rics.bwh.harvard.edu
Published
2011-01-00
Epub
2010-00-21
Pages
262-73
Language
English
Region
England
NLM ID
0204634
PMCID
PMC2996483
Subset
IM
Grants
NCI NIH HHS · P01CA 119070 · United States
NCI NIH HHS · R01 CA092433 · United States
NCI NIH HHS · R01CA092433 · United States
NCI NIH HHS · P01 CA119070-01A1 · United States
NIAID NIH HHS · R01 AI047833 · United States
NCI NIH HHS · P01 CA119070-050001 · United States
NCI NIH HHS · P01 CA119070-05 · United States
NIAID NIH HHS · R01AI047833 · United States
NCI NIH HHS · P01 CA119070 · United States
External Links
PubMed source DOI: 10.1002/path.2789 PMC Full Text View journal details
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