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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1262-1270. Prepublished online as a Blood First Edition Paper on April 24, 2007; DOI 10.1182/blood-2006-04-015826. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2006-04-015826v1 110/4/1262    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 Mead, A. J Articles by Gale, R. E Search for Related Content PubMed PubMed Citation Articles by Mead, A. J Articles by Gale, R. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 11, 2006 Accepted April 19, 2007 FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia Adam J Mead*, David C Linch, Robert K Hills, Keith Wheatley, Alan K Burnett, and Rosemary E Gale Department of Haematology, Royal Free and University College Medical School, London, United Kingdom Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom * Corresponding author; email: adam.mead{at}ucl.ac.uk. The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently uncertain. To resolve this issue we screened 1107 young adult non-acute promyelocytic leukemia AML patients with known FLT3 internal tandem duplication (ITD) status for FLT3/TKDs; they were detected in 127 (11%) cases. Mutations were associated with a high white cell count (P=.006) and patients with inv(16) (P=.005), but were infrequent in patients with adverse cytogenetics and secondary AML. Overall survival (OS) at 5 years was 53% and 37% for FLT3/TKD mutant and wild type patients respectively (odds ratio 0.72, 95% confidence intervals 0.58-0.89, P=.002). For both the cumulative incidence of relapse and OS the difference in outcome between FLT3/ITDs and FLT3/TKDs was highly significant (P<.0001). In multivariate analysis, impact of FLT3/TKDs on OS when including all mutant-positive patients was not significant, but patients with high level mutations (more than 25% mutant) had a significantly improved outcome (P=.004). The novel finding that biologically distinct activating mutations of the same gene can be associated with markedly different clinical outcomes has implications for risk stratification and therapy, and is significant to the understanding of chemo-resistance in AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. V. Tiu, L. P. Gondek, C. L. O'Keefe, J. Huh, M. A. Sekeres, P. Elson, M. A. McDevitt, X. F. Wang, M. J. Levis, J. E. Karp, et al. New Lesions Detected by Single Nucleotide Polymorphism Array-Based Chromosomal Analysis Have Important Clinical Impact in Acute Myeloid Leukemia J. Clin. Oncol., November 1, 2009; 27(31): 5219 - 5226. [Abstract] [Full Text] [PDF] K. H. Metzeler, A. Dufour, T. Benthaus, M. Hummel, M.-C. Sauerland, A. Heinecke, W. E. Berdel, T. Buchner, B. Wormann, U. Mansmann, et al. 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