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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 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 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 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. Related Collections Oncogenes and Tumor Suppressors Signal Transduction Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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. Mead1, David C. Linch1, Robert K. Hills2, Keith Wheatley3, Alan K. Burnett2, and Rosemary E. Gale1 1 Department of Haematology, Royal Free and University College Medical School, London, United Kingdom; 2 Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom; and 3 Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom, on behalf of the National Cancer Research Institute (NCRI) Adult Leukaemia Working Party, United Kingdom 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 nonacute 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 interval, 0.58 to 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 < .001). 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 chemoresistance in AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. Mead, R. E. Gale, R. K. Hills, M. Gupta, B. D. Young, A. K. Burnett, and D. C. Linch Conflicting data on the prognostic significance of FLT3/TKD mutations in acute myeloid leukemia might be related to the incidence of biallelic disease Blood, July 15, 2008; 112(2): 444 - 445. [Full Text] [PDF] S. P. Whitman, G. Marcucci, A. S. Ruppert, K. Mrozek, and C. D. Bloomfield Response: Conflicting data on the prognostic significance of FLT3-TKD mutations in cytogenetically normal acute myeloid leukemia (CN-AML) might be related to many factors, including techniques used to detect FLT3-TKD, differences in patient populations studied, and treatment regimens Blood, July 15, 2008; 112(2): 445 - 445. [Full Text] [PDF] R. F. Schlenk, K. Dohner, J. Krauter, S. Frohling, A. Corbacioglu, L. Bullinger, M. Habdank, D. Spath, M. Morgan, A. Benner, et al. Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1909 - 1918. [Abstract] [Full Text] [PDF] L. Bullinger, K. Dohner, R. Kranz, C. Stirner, S. Frohling, C. Scholl, Y. H. Kim, R. F. Schlenk, R. Tibshirani, H. Dohner, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML Blood, May 1, 2008; 111(9): 4490 - 4495. [Abstract] [Full Text] [PDF] M. Levis Who's dancing with FLT3? Blood, March 1, 2008; 111(5): 2503 - 2504. [Full Text] [PDF] U. Bacher, C. Haferlach, W. Kern, T. Haferlach, and S. Schnittger Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients Blood, March 1, 2008; 111(5): 2527 - 2537. [Abstract] [Full Text] [PDF] S. P. Whitman, A. S. Ruppert, M. D. Radmacher, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, F. Racke, B. L. Powell, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications Blood, February 1, 2008; 111(3): 1552 - 1559. [Abstract] [Full Text] [PDF] H. Dohner Implication of the Molecular Characterization of Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 412 - 419. [Abstract] [Full Text] [PDF]

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