Searching across hundreds of databases
Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34+ stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML.
Pubmed ID: 28844837 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Collection of genome-wide transcriptional expression data from cultured human cells treated with bioactive small molecules and simple pattern-matching algorithms. camp aims to enable the discovery of functional connections between drugs, genes and diseases through the transitory feature of common gene-expression changes.
View all literature mentionsThis polyclonal targets Rabbit F(ab)2 IgG
View all literature mentionsThis polyclonal targets Prostaglandin E Receptor EP4
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets CD45R (B220)
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD33
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis polyclonal targets Prostaglandin E Receptor EP2 antibody (Phycoerythrin)
View all literature mentionsThis monoclonal targets beta-Catenin
View all literature mentionsThis monoclonal targets CD117
View all literature mentionsThis monoclonal targets Ly-6A/E (Sca-1)
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsMus musculus with name B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J from IMSR.
View all literature mentions
Mus musculus with name B6.SJL-Ptprca Pepc
Mus musculus with name B6.129-Ctnnb1tm2Kem/KnwJ from IMSR.
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
