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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2929-2935. Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-10-3443. This Article Full Text (PDF) All Versions of this Article: 2003-10-3443v1 103/8/2929    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 Bono, P. Articles by Joensuu, H. Search for Related Content PubMed PubMed Citation Articles by Bono, P. Articles by Joensuu, H. Social Bookmarking                   What's this? Submitted October 8, 2003 Accepted December 29, 2003 Serum KIT and KIT ligand levels in gastrointestinal stromal tumor patients treated with imatinib Petri Bono, Andreas Krause, Margaret von Mehren, Michael C Heinrich, Charles D Blanke, Sasa Dimitrijevic, George D Demetri, and Heikki Joensuu* Dept. of Oncology, Helsinki University Central Hospital, Helsinki, Finland Oregon Health & Science University Cancer Institute and Portland Veterans Affairs Medical Center, OHSU Cancer Institute, Portland, OR, USA Fox-Chase Cancer Center, Philadelphia, PA, USA Harvard Cancer Center, Dana-Farber Cancer Institue, Boston, MA, USA Novartis Oncology, East Hanover, NJ, USA Novartis Oncology, Basel, Switzerland * Corresponding author; email: heikki.joensuu{at}hus.fi. Imatinib is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). We monitored the serum levels of KIT, KIT ligand (stem cell factor, SCF), and the vascular endothelial growth factor (VEGF) in patients with advanced GIST treated with imatinib in a prospective randomized trial. GIST patients (n=66) had elevated pretreatment serum KIT and VEGF levels as compared with controls (median, 292 AU/mL vs. 238 AU/mL, P = .037; and median, 303 pg/mL vs. 190 pg/mL, P = .013, respectively), but lower levels of SCF (median, 645 pg/mL vs. 950 pg/mL; P = < .0001). After one and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from the pretreatment level, whereas SCF increased 11% and 33%, respectively. Serum VEGF levels decreased during treatment in responding patients. The median serum SCF/KIT ratio increased with treatment duration, and was 7.7-fold higher following 12 months of treatment than at baseline (range 3.1-259). A high serum SCF-to-KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mithraprabhu and K. L Loveland Control of KIT signalling in male germ cells: what can we learn from other systems? Reproduction, November 1, 2009; 138(5): 743 - 757. [Abstract] [Full Text] [PDF] C. D. Blanke Biomarkers in GIST: Partly Ready for Prime-Time Use Clin. Cancer Res., September 15, 2009; 15(18): 5603 - 5605. [Abstract] [Full Text] [PDF] S. E. DePrimo, X. Huang, M. E. Blackstein, C. R. Garrett, C. S. Harmon, P. Schoffski, M. H. Shah, J. Verweij, C. M. Baum, and G. D. Demetri Circulating Levels of Soluble KIT Serve as a Biomarker for Clinical Outcome in Gastrointestinal Stromal Tumor Patients Receiving Sunitinib following Imatinib Failure Clin. Cancer Res., September 15, 2009; 15(18): 5869 - 5877. [Abstract] [Full Text] [PDF] N. Lassau, M. Lamuraglia, L. Chami, J. Leclere, S. Bonvalot, P. Terrier, A. Roche, and A. Le Cesne Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. Am. J. Roentgenol., November 1, 2006; 187(5): 1267 - 1273. [Abstract] [Full Text] [PDF] E. Wardelmann, S. Merkelbach-Bruse, K. Pauls, N. Thomas, H.-U. Schildhaus, T. Heinicke, N. Speidel, T. Pietsch, R. Buettner, D. Pink, et al. Polyclonal Evolution of Multiple Secondary KIT Mutations in Gastrointestinal Stromal Tumors under Treatment with Imatinib Mesylate. Clin. Cancer Res., March 15, 2006; 12(6): 1743 - 1749. [Abstract] [Full Text] [PDF] M. C. Heinrich, G. A. McArthur, G. D. Demetri, H. Joensuu, P. Bono, R. Herrmann, H. Hirte, S. Cresta, D. B. Koslin, C. L. Corless, et al. Clinical and Molecular Studies of the Effect of Imatinib on Advanced Aggressive Fibromatosis (desmoid tumor) J. Clin. Oncol., March 1, 2006; 24(7): 1195 - 1203. [Abstract] [Full Text] [PDF]

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