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Blood, 1 July 2007, Vol. 110, No. 1, pp. 323-333. Prepublished online as a Blood First Edition Paper on April 13, 2007; DOI 10.1182/blood-2006-10-052282. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-052282v1 blood-2006-10-052282v2 110/1/323    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Gu, T.-l. Articles by Polakiewicz, R. D. Search for Related Content PubMed PubMed Citation Articles by Gu, T.-l. Articles by Polakiewicz, R. D. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia Ting-lei Gu1, Thomas Mercher2, Jeffrey W. Tyner3, Valerie L. Goss1, Denise K. Walters3, Melanie G. Cornejo2, Cynthia Reeves1, Lana Popova1, Kimberly Lee1, Michael C. Heinrich3, John Rush1, Masanori Daibata4, Isao Miyoshi4, D. Gary Gilliland2, Brian J. Druker3, and Roberto D. Polakiewicz1 1 Cell Signaling Technology, Danvers, MA; 2 Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; 3 Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health & Science University Cancer Institute, Portland, OR; 4 Department of Medicine, Kochi Medical School, Kochi University, Japan Activated tyrosine kinases have been frequently implicated in the pathogenesis of cancer, including acute myeloid leukemia (AML), and are validated targets for therapeutic intervention with small-molecule kinase inhibitors. To identify novel activated tyrosine kinases in AML, we used a discovery platform consisting of immunoaffinity profiling coupled to mass spectrometry that identifies large numbers of tyrosine-phosphorylated proteins, including active kinases. This method revealed the presence of an activated colony-stimulating factor 1 receptor (CSF1R) kinase in the acute megakaryoblastic leukemia (AMKL) cell line MKPL-1. Further studies using siRNA and a small-molecule inhibitor showed that CSF1R is essential for the growth and survival of MKPL-1 cells. DNA sequence analysis of cDNA generated by 5'RACE from CSF1R coding sequences identified a novel fusion of the RNA binding motif 6 (RBM6) gene to CSF1R gene generated presumably by a t(3;5)(p21;q33) translocation. Expression of the RBM6-CSF1R fusion protein conferred interleukin-3 (IL-3)–independent growth in BaF3 cells, and induces a myeloid proliferative disease (MPD) with features of megakaryoblastic leukemia in a murine transplant model. These findings identify a novel potential therapeutic target in leukemogenesis, and demonstrate the utility of phosphoproteomic strategies for discovery of tyrosine kinase alleles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. W. Tyner, D. K. Walters, S. G. Willis, M. Luttropp, J. Oost, M. Loriaux, H. Erickson, A. S. Corbin, T. O'Hare, M. C. Heinrich, et al. RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2238 - 2245. [Abstract] [Full Text] [PDF]

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