Scientific Publications

Proteomic and genetic approaches identify Syk as an AML target.

Publication TypeJournal Article
AuthorsHahn, CK, Berchuck JE, Ross KN, Kakoza RM, Clauser K., Schinzel AC, Ross L., Galinsky I., Davis TN, Silver SJ, Root DE, Stone RM, DeAngelo DJ, Carroll M., Hahn WC, Carr SA, Golub T. R., Kung AL, and Stegmaier K.
AbstractCell-based screening can facilitate the rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires the identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target, anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer.
Year of Publication2009
JournalCancer cell
Volume16
Issue4
Pages281-94
Date Published (YYYY/MM/DD)2009/10/06
ISSN Number1535-6108
DOI10.1016/j.ccr.2009.08.018
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/19800574?dopt=Abstract