Targeting cell cycle and apoptosis to overcome chemoresistance in AML

A genome-wide CRISPR knockout screen investigating resistance to doxorubicin and cytarabine (Dox/AraC) in human AML cell lines identified gene knockout of cyclin dependent kinase inhibitor 2A (CDKN2A) as contributing to resistance. To investigate the therapeutic potential of upregulating CDKN2A expression using WM-1119 and further elucidate its mechanism of action, we performed RNA-seq on WM-1119- (or vehicle control) treated OCI-AML3 cells with or without CRISPR mediated genetic depletion of CDKN2A. Comparative gene expression profiling analysis of RNA-seq data for OCI-AML3 cells with and without CDKN2A depletion treated with WM-1119 at 1 uM or vehicle control for 7 days.