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Series GSE6396 Query DataSets for GSE6396
Status Public on Dec 02, 2006
Title Targeting the NF-κB signaling pathway in Notch1-induced T cell leukemia
Organism Mus musculus
Experiment type Expression profiling by array
Summary T cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that the majority of TALL patients 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-κB pathway transcriptionally and via the IκB kinase (IKK) complex, thereby causing increased expression of multiple well-characterized NF-κB target genes in bone marrow hematopoietic stem cells and progenitors. Our observations demonstrate that the NF-κB 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 studies identify NF-κB as one of the major mediators of NOTCH1-induced transformation and suggest that the NF-κB pathway is a potential target of future targeted therapies of T-ALL.
Keywords: gene expression analysis, signaling pathway alteration
 
Overall design Number of samples: 2.
Replicates: no.
Dye swaps: yes (Cy3, Cy5).
Reference sample: 1.
 
Contributor(s) Vilimas T, Aifantis I
Citation(s) 17173050
Submission date Nov 29, 2006
Last update date Mar 16, 2012
Contact name Tomas Vilimas
E-mail(s) tomas.x.vilimas@gsk.com, tvilimas@gmail.com
Phone 1-610-917-5855
Organization name GlaxoSmithKline
Department Oncology Discovery Technology Group
Street address 1250 S. Collegeville Rd.
City Collegeville
State/province PA
ZIP/Postal code 19403
Country USA
 
Platforms (1)
GPL4596 Vilimas (Agilent Mouse Microarray G4121A)
Samples (3)
GSM147443 EGFP-expressing BM progenitors vs Notch1-IC-expressing BM progenitors
GSM147464 EGFP-expressing BM progenitors vs Notch1-IC-expressing BM progenitors cultured on OP9-DL1 stroma
GSM147508 Notch1-IC-expressing BM progenitors vs Notch1-IC-expressing BM progenitors cultured on OP9-DL1 stroma
Relations
BioProject PRJNA99707

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE6396_RAW.tar 31.0 Mb (http)(custom) TAR (of TXT)

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