Characterization of MYC expression in gefitinib versus Acute Myeloid Leukemia reveals novel therapeutic targets

We conducted gene expression profiling and pathway analysis of microarray data generated from a gefitinib versus M4-AML study. Our findings indicate that a therapeutic reduction of the human v-Myc oncoprotein correlated to molecular reversal of cell transformation within 24 hours of treatment. We analyzed the known efficacies of gefitinib and were able to identify bona fide gefitinib targets in the PDGFR pathway that we believe to be responsible for cell rescue. These targets, Src and Jnk3, demonstrated strong interactions with gefitinib in small molecule/tyrosine kinase binding assays and have proven critical to MYC induction in gene inhibition assays.