|
Comments
|
This is an acute myeloid leukemia (AML) IDH2R140Q mutant isogenic line derived from the parental TF-1 cell line. The c.419G>A knock-in mutation encoding IDH2R140Q protein expression was generated at ATCC by utilizing the CRISPR/Cas9 gene editing technology. This is a homozygous mutation expressing the c.419G>A mutant allele. The IDH2R140Q mutation in CRL-2003IG has been validated at the genomic, transcript, and protein bio-functional levels.
The IDH2R140Q mutation is a cancer driver gene which causes a gain of function in tumor cells converting isocitrate to the oncometabolite, D-2-hydroxyglutarate (D-2HG). High intracellular levels of D-2HG inhibits alpha-ketoglutarate-dependent DNA and histone demethylases, resulting in epigenetic disregulation, which in turn leads to a block in cellular differentiation, promoting AML development. These effects are reduced with treatment of IDH2 mutant-specific small-molecule inhibitors such as AG-221.
The IDH2R140Q mutant isogenic line CRL-2003IG has been tested for neomorphic functional activity displaying elevated intra- and extracellular D-2HG levels. A reduction in histone hypermethylation was also observed upon treatment with IDH2 specific molecules, AG-221 and AGI-6780. This IDH2R140Q isogenic cell model is a valuable in vitro cell-based tool for clinical diagnostics, elucidating mechanisms involved in cancer-associated differentiation, tumorigenesis and use in screening anti-cancer compounds for drug discovery and development.
Refer to the TF-1 parental line (ATCC CRL-2003) for additional background information.
|