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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1791-1799. Prepublished online as a Blood First Edition Paper on October 27, 2005; DOI 10.1182/blood-2005-04-1466. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1466v1 107/5/1791    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 Schnittger, S. Articles by Schoch, C. Search for Related Content PubMed PubMed Citation Articles by Schnittger, S. Articles by Schoch, C. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival Susanne Schnittger, Tobias M. Kohl, Torsten Haferlach, Wolfgang Kern, Wolfgang Hiddemann, Karsten Spiekermann, and Claudia Schoch From the Laboratory of Leukemia Diagnostics and the Clinical Cooperative group "Leukemia," Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians University, Munich; and the GSF-National Research Center for Environment and Health, Munich, Germany. Mutations in codon D816 of the KIT gene represent a recurrent genetic alteration in acute myeloid leukemia (AML). To clarify the biologic implication of activation loop mutations of the KIT gene, 1940 randomly selected AML patients were analyzed. In total, 33 (1.7%) of 1940 patients were positive for D816 mutations. Of these 33 patients, 8 (24.2%) had a t(8;21), which was significantly higher compared with the subgroup without D816 mutations. Analyses of genetic subgroups showed that KIT-D816 mutations were associated with t(8;21)/AML1-ETO and other rare AML1 translocations. In contrast, other activating mutations like FLT3 and NRAS mutations were very rarely detected in AML1-rearranged leukemia. KIT mutations had an independent negative impact on overall (median 304 vs 1836 days; P = .006) and event-free survival (median 244 vs 744 days; P = .003) in patients with t(8;21) but not in patients with a normal karyotype. The KIT-D816V receptor expressed in Ba/F3 cells was resistant to growth inhibition by the selective PTK inhibitors imatinib and SU5614 but fully sensitive to PKC412. Our findings clearly indicate that activating mutations of receptor tyrosine kinases are associated with distinct genetic subtypes in AML. The KIT-D816 mutations confer a poor prognosis to AML1-ETO-positive AML and should therefore be included in the diagnostic workup. Patients with KIT-D816-positive/AML1-ETO-positive AML might benefit from early intensification of treatment or combination of conventional chemotherapy with KIT PTK inhibitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Edwards, C. Xie, K. M. LaFiura, A. A. Dombkowski, S. A. Buck, J. L. Boerner, J. W. Taub, L. H. Matherly, and Y. Ge RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia Blood, September 24, 2009; 114(13): 2744 - 2752. [Abstract] [Full Text] [PDF] T. Akagi, L.-Y. Shih, S. Ogawa, J. Gerss, S. R. Moore, R. Schreck, N. Kawamata, D.-C. Liang, M. Sanada, Y. Nannya, et al. 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