Ghent University Academic Bibliography

Advanced

A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia

Apostolos Klinakis, Camille Lobry, Omar Abdel-Wahab, Philmo Oh, Hiroshi Haeno, Silvia Buonamici, Inge van De Walle, Severine Cathelin, Thomas Trimarchi, Elisa Araldi, et al. (2011) NATURE. 473(7346). p.230-233
abstract
Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multisubunit gamma-secretase (gamma SE) complex(2). Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations(3). Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SPECIFICATION, DIFFERENTIATION, MICE, T-CELL DEVELOPMENT, ACTIVATION, EXPRESSION, PROGENITOR, COMPLEX
journal title
NATURE
Nature
volume
473
issue
7346
pages
230 - 233
Web of Science type
Article
Web of Science id
000290487200042
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
36.28 (2011)
JCR rank
1/54 (2011)
JCR quartile
1 (2011)
ISSN
0028-0836
DOI
10.1038/nature09999
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2099742
handle
http://hdl.handle.net/1854/LU-2099742
date created
2012-05-07 12:05:52
date last changed
2016-12-19 15:42:57
@article{2099742,
  abstract     = {Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multisubunit gamma-secretase (gamma SE) complex(2). Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations(3). Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue.},
  author       = {Klinakis, Apostolos and Lobry, Camille and Abdel-Wahab, Omar and Oh, Philmo and Haeno, Hiroshi and Buonamici, Silvia and van De Walle, Inge and Cathelin, Severine and Trimarchi, Thomas and Araldi, Elisa and Liu, Cynthia and Ibrahim, Sherif and Beran, Miroslav and Zavadil, Jiri and Efstratiadis, Argiris and Taghon, Tom and Michor, Franziska and Levine, Ross L and Aifantis, Iannis},
  issn         = {0028-0836},
  journal      = {NATURE},
  keyword      = {SPECIFICATION,DIFFERENTIATION,MICE,T-CELL DEVELOPMENT,ACTIVATION,EXPRESSION,PROGENITOR,COMPLEX},
  language     = {eng},
  number       = {7346},
  pages        = {230--233},
  title        = {A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia},
  url          = {http://dx.doi.org/10.1038/nature09999},
  volume       = {473},
  year         = {2011},
}

Chicago
Klinakis, Apostolos, Camille Lobry, Omar Abdel-Wahab, Philmo Oh, Hiroshi Haeno, Silvia Buonamici, Inge van De Walle, et al. 2011. “A Novel Tumour-suppressor Function for the Notch Pathway in Myeloid Leukaemia.” Nature 473 (7346): 230–233.
APA
Klinakis, A., Lobry, C., Abdel-Wahab, O., Oh, P., Haeno, H., Buonamici, S., van De Walle, I., et al. (2011). A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. NATURE, 473(7346), 230–233.
Vancouver
1.
Klinakis A, Lobry C, Abdel-Wahab O, Oh P, Haeno H, Buonamici S, et al. A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. NATURE. 2011;473(7346):230–3.
MLA
Klinakis, Apostolos, Camille Lobry, Omar Abdel-Wahab, et al. “A Novel Tumour-suppressor Function for the Notch Pathway in Myeloid Leukaemia.” NATURE 473.7346 (2011): 230–233. Print.