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

(2011) NATURE. 473(7346). p.230-233
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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.
Keywords
SPECIFICATION, DIFFERENTIATION, MICE, T-CELL DEVELOPMENT, ACTIVATION, EXPRESSION, PROGENITOR, COMPLEX

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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.
@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},
}

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