Systematic name M5319
Brief description Genes up-regulated by imatinib [PubChem=5291] during dendritic cell differentiation.
Full description or abstract Dendritic cells are the most powerful antigen-presenting cells playing a decisive role for the initiation and maintenance of primary immune responses. However, signaling pathways involved in the differentiation of these cells have not been fully determined. Imatinib is a novel tyrosine kinase inhibitor effective against Abl kinases, c-Kit, and platelet-derived growth factor receptor. Using this compound, we show that human monocyte-derived dendritic cells generated in the presence of therapeutic concentrations of imatinib show a reduced expression of CD1a, MHC class I and II, and costimulatory molecules as well as decreased secretion of chemokines and cytokines resulting in an impaired capacity of dendritic cells to elicit primary T-cell responses. Using Western blot analyses, we found that these effects are mediated by inhibition of phosphatidylinositol 3-kinase/Akt pathways and a pronounced down-regulation of nuclear localized protein levels of nuclear factor-kappaB family members. Importantly, using blocking antibodies and tyrosine kinase inhibitors, we show that the inhibitory effects of imatinib on dendritic cell differentiation are not mediated via platelet-derived growth factor receptor and c-Kit. Taken together, our study reveals that imatinib inhibits dendritic cell differentiation and function via Akt and nuclear factor-kappaB signal transduction. Importantly, we show that imatinib can inhibit the function of normal, nonmalignant cells that may result in immunosuppression of these patients.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15756019   Authors: Appel S,Rupf A,Weck MM,Schoor O,Brümmendorf TH,Weinschenk T,Grünebach F,Brossart P
Exact source Table 3
Related gene sets  
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform Human_RefSeq
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 33 genes
Gene families Categorize these 33 genes by gene family
Show members (show 33 members mapped to 33 genes)
Version history 3.0: Renamed from APPEL_IMATINIB_UP

See MSigDB license terms here. Please note that certain gene sets have special access terms.