STANDARD_NAME	VILIMAS_NOTCH1_TARGETS_UP
SYSTEMATIC_NAME	M1869
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VILIMAS_NOTCH1_TARGETS_UP
NAMESPACE	MOUSE_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in bone marrow progenitors by constitutively active NOTCH1 [GeneID=4851].
DESCRIPTION_FULL	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.
PMID	17173050
GEOID	GSE6396
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
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig 1a, 1BS, 1CS: up in either early or late
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	Bcl2a1,Birc2,Birc3,Card11,Ccl5,Ccr7,Cd127,Cd2,Cd25,Cd28,Cd3d,Cd3g,Cd69,Cd7,Cd74,Cd80,Cd83,Cd86,Ctla4,Cx3cl1,Ddr1,Dtx1,Egr1,Egr2,Gata3,Gzma,Gzmb,Gzmc,Gzmd,Hey1,Icam1,Id2,Il10ra,Il12b,Irf7,Junb,Lat,Lck,Nfatc1,Nfkb2,Nfkbia,Notch3,Nrarp,P2ry10,Ptcra,Rag1,Rag2,Relb,Rras2,Tcrb-J,Tcrb-V,Tcrd-D,Tcrg-C,Tcrg-V,Tcrim,Thy1,Tnfrsf18,Tox,Traf1,Zap70
GENE_SYMBOLS	BCL2A1,BIRC2,BIRC3,CARD11,CCL5,CCR7,,CD2,,CD28,CD3D,CD3G,CD69,CD7,CD74,CD80,CD83,CD86,CTLA4,CX3CL1,DDR1,DTX1,EGR1,EGR2,GATA3,GZMA,GZMB,GZMB,,HEY1,ICAM1,ID2,IL10RA,IL12B,IRF7,JUNB,LAT,LCK,NFATC1,NFKB2,NFKBIA,NOTCH3,NRARP,P2RY10,PTCRA,RAG1,RAG2,RELB,RRAS2,,,,,,TRAT1,THY1,TNFRSF18,TOX,TRAF1,ZAP70
FOUNDER_NAMES