| First Author | Vilimas T | Year | 2007 |
| Journal | Nat Med | Volume | 13 |
| Issue | 1 | Pages | 70-7 |
| PubMed ID | 17173050 | Mgi Jnum | J:129585 |
| Mgi Id | MGI:3769820 | Doi | 10.1038/nm1524 |
| Citation | Vilimas T, et al. (2007) Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med 13(1):70-7 |
| abstractText | T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced neoplastic transformation remain undefined. We report here that constitutively active Notch1 activates the NF-kappaB pathway transcriptionally and via the IkappaB kinase (IKK) complex, thereby causing increased expression of several well characterized target genes of NF-kappaB in bone marrow hematopoietic stem cells and progenitors. Our observations demonstrate that the NF-kappaB pathway is highly active in established human T-ALL and that inhibition of the pathway can efficiently restrict tumor growth both in vitro and in vivo. These findings identify NF-kappaB as one of the major mediators of Notch1-induced transformation and suggest that the NF-kappaB pathway is a potential target of future therapies of T-ALL. |
