Gene Set: VILIMAS_NOTCH1_TARGETS_DN

Standard name VILIMAS_NOTCH1_TARGETS_DN
Systematic name M1873
Brief description Genes down-regulated in bone marrow progenitors by constitutively active NOTCH1 [GeneID=4851].
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17173050   Authors: Vilimas T,Mascarenhas J,Palomero T,Mandal M,Buonamici S,Meng F,Thompson B,Spaulding C,Macaroun S,Alegre ML,Kee BL,Ferrando A,Miele L,Aifantis I
Exact source Fig 1a, 1BS, 1CS: down in either early or late
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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