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

Author

Courage, James F. ; Gupta, Saurabh ; Wang, Yufeng

Author_Institution

Inst. for Drug Dev., San Antonio

fYear

2007

fDate

14-17 Oct. 2007

Firstpage

699

Lastpage

706

Abstract

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.

Keywords

biochemistry; blood; cellular biophysics; diseases; drugs; enzymes; genetics; medical computing; microorganisms; molecular biophysics; MYC expression; acute myeloid leukemia; binding assays; cell transformation; gefitinib; gene expression profiling; gene inhibition assays; microarray data; myelocytomatosis viral oncogene homolog; oncoprotein; pathway analysis; therapeutic targets; tyrosine kinase; Amino acids; Bones; Cancer; Data analysis; Drugs; Gene expression; Hemorrhaging; Humans; Medical treatment; White blood cells; Acute Myeloid Leukemia; Gefitinib; JNK3; MYC; Microarray; P38; SRC;

fLanguage

English

Publisher

ieee

Conference_Titel

Bioinformatics and Bioengineering, 2007. BIBE 2007. Proceedings of the 7th IEEE International Conference on

Conference_Location

Boston, MA

Print_ISBN

978-1-4244-1509-0

Type

conf

DOI

10.1109/BIBE.2007.4375637

Filename

4375637