This line has been tested in parallel with its parental line at the genomic, transcript and cellular levels as well as assayed for the desired phenotypic functional activity resembling the intended genotypic IDH2R140Q knock-in mutation. Elevated 2-hydroxyglutarate or (2-HG) levels in the IDH2R140Q mutant isogenic line are observed, above the WT parental cell line, and hypermethylation detected by western blotting for H3K4me3 and H3K27me3 histone markers.
The IDH2R140Q acute myeloid leukemia isogenic line was tested with two IDH2 specific inhibitors: AGI-6780 and AG-221. A reduction in histone methylation compared to the untreated and DMSO groups was observed. In addition, the 2-hydroxyglutarate (2-HG) levels in our WT parental samples were unaffected by the drug treatment whereas the IDH2R140Q isogenic mutant showed remarkably high levels of 2-HG secreted in untreated and DMSO control treated groups and a reduction in the 2-HG levels when treated with AGI-6780 and AG-221.
|Date Created||10/03/2017 12:04 PM
|Date Updated||10/03/2017 12:05 PM