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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2238-2245. Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-06-097253. This Article Full Text (PDF) Supplemental Appendix, Tables, and Figures All Versions of this Article: blood-2007-06-097253v1 111/4/2238    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tyner, J. W Articles by Druker, B. J Search for Related Content PubMed PubMed Citation Articles by Tyner, J. W Articles by Druker, B. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 21, 2007 Accepted November 12, 2007 RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia Jeffrey W Tyner, Denise K Walters, Stephanie G Willis, Mary Luttropp, Jason Oost, Marc Loriaux, Heidi Erickson, Amie S Corbin, Thomas O'Hare, Michael C Heinrich, Michael W Deininger, and Brian J Druker* Division of Hematology and Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, OR, United States Howard Hughes Medical Institute, Portland, OR, United States Department of Pathology, Oregon Health & Science University, Portland, OR, United States Portland VA Medical Center, Portland, OR, United States * Corresponding author; email: druker{at}ohsu.edu. Despite vast improvements in our understanding of cancer genetics, a large percentage of cancer cases present without knowledge of the causative genetic events. Tyrosine kinases are frequently implicated in the pathogenesis of numerous types of cancer, but identification and validation of tyrosine kinase targets in cancer can be a time-consuming process. We report the establishment of an efficient, functional screening assay using RNAi technology to directly assess and compare the effect of individually targeting each member of the tyrosine kinase family. We demonstrate that siRNA screening can identify tyrosine kinase targets containing activating mutations in Janus kinase (JAK) 3 (A572V) in CMK cells and c-KIT (V560G) in HMC1.1 cells. In addition, this assay identifies targets that do not contain mutations, such as JAK1 and the focal adhesion kinases (FAK), that are crucial to the survival of the cancer cells. This technique, with additional development, may eventually offer the potential to match specific therapies with individual patients based on a functional assay. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. C. P. Cross Hitchhikers' guide to the leukemia genome Blood, May 1, 2008; 111(9): 4428 - 4429. [Full Text] [PDF]

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