Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Nature | May 12, 2011

Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types. Its activity is controlled by the multi-subunit γ-secretase (γSE) complex. 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. 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.

Pubmed ID: 21562564 RIS Download

Mesh terms: Animals | Basic Helix-Loop-Helix Transcription Factors | Cell Differentiation | Cells, Cultured | Gene Expression Profiling | Gene Expression Regulation, Neoplastic | Gene Silencing | Genes, Tumor Suppressor | Granulocyte-Macrophage Progenitor Cells | Hematopoietic Stem Cells | Homeodomain Proteins | Humans | Leukemia, Myelomonocytic, Chronic | Mice | Mice, Inbred C57BL | Mutation | Receptors, Notch | Signal Transduction | Transcription Factor HES-1 | Tumor Cells, Cultured

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: 1P01CA97403
  • Agency: NCI NIH HHS, Id: U54 CA143798
  • Agency: NCI NIH HHS, Id: P01 CA097403
  • Agency: NCI NIH HHS, Id: R01 CA133379
  • Agency: NCI NIH HHS, Id: R01CA133379
  • Agency: NCI NIH HHS, Id: R21CA141399
  • Agency: NCI NIH HHS, Id: R01 CA149655
  • Agency: Howard Hughes Medical Institute, Id: HHMI_AIFANTIS_I
  • Agency: NCI NIH HHS, Id: R01 CA105129
  • Agency: NCI NIH HHS, Id: R01 CA133379-04
  • Agency: NCI NIH HHS, Id: R01CA1328234
  • Agency: NCI NIH HHS, Id: R21 CA141399-02
  • Agency: NCI NIH HHS, Id: R21 CA141399
  • Agency: NCI NIH HHS, Id: R01CA149655
  • Agency: NCI NIH HHS, Id: R01 CA105129-07
  • Agency: NCI NIH HHS, Id: U54CA143798
  • Agency: NCI NIH HHS, Id: R01CA105129
  • Agency: NCI NIH HHS, Id: R01 CA149655-03

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Broad Institute

A biomedical and genomic research center that is independently governed that encompasses three types of organizational units: core member laboratories, programs and platforms which work together and with other collaborators to tackle critical problems in human biology and disease. Data and cutting edge software tools are generated and developed, and these tools analyze those data (increasingly large genome-related datasets) which is shared openly with the scientific community. The Broad faculty includes core members and associate members. All associate members hold primary appointments in a home department at one of the partner institutions, but are deeply involved in the scientific work and culture of the Broad Institute. It is formally affiliated with the Massachusetts Institute of Technology, Harvard University and its affiliated hospitals.

tool

View all literature mentions

Gene Expression Omnibus

A public functional genomics data repository supporting MIAME-compliant data submissions. Tools are provided to help users query and download experiments and curated gene expression profiles. These data include microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted.

tool

View all literature mentions