| First Author | Klinakis A | Year | 2011 |
| Journal | Nature | Volume | 473 |
| Issue | 7346 | Pages | 230-3 |
| PubMed ID | 21562564 | Mgi Jnum | J:172442 |
| Mgi Id | MGI:5007845 | Doi | 10.1038/nature09999 |
| Citation | Klinakis A, et al. (2011) A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473(7346):230-3 |
| abstractText | Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types. Its activity is controlled by the multi-subunit gamma-secretase (gammaSE) 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. |
