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Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4326-4335 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis Christian Thiede, Christine Steudel, Brigitte Mohr, Markus Schaich, Ulrike Schäkel, Uwe Platzbecker, Martin Wermke, Martin Bornhäuser, Markus Ritter, Andreas Neubauer, Gerhard Ehninger, and Thomas Illmer From the Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der Technischen Universität, Dresden; and the Abteilung Hämatologie, Onkologie und Immunologie, Philipps Universität Marburg, Germany. Constitutive activation of the FLT3 receptor tyrosine kinase, either by internal tandem duplication (ITD) of the juxtamembrane region or by point mutations in the second tyrosine kinase domain (TKD), has been described in patients with acute myelogenous leukemia (AML). We analyzed the prevalence and the potential prognostic impact of FLT3 mutations in 979 AML patients. Results were correlated with cytogenetic data and the clinical response. FLT3-ITD mutations were found in 20.4% and FLT3-TKD mutations in 7.7% of the patients. Each mutation was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype. Significantly more FLT3 aberrations were found in patients with FAB M5, and fewer were found in patients with FAB M2 and M6. Although less frequent in patients with cytogenetic aberrations, FLT3-ITDs were found in 13 of 42 patients with t(15;17) and in 9 of 10 patients with t(6;9). The prevalence of the ITD allele on the DNA level was heterogeneous, ranging from faint mutant bands in some patients to predominant mutant bands in others. Based on quantitative analysis, the mutant-wild-type (wt) ratio ranged from 0.03 to 32.56 (median, 0.78). Patients with a high mutant/wt ratio (ie, greater than 0.78) had significantly shorter overall and disease-free survival, whereas survival in patients with ratios below 0.78 did not differ from those without FLT3 aberrations. Multivariate analysis confirmed a high mutant/wt ratio to be a strong independent prognostic factor. Taken together, these data confirm that FLT mutations represent a common alteration in adult AML. Constitutive activation may be associated with monocytoid differentiation. A high mutant/wt ratio in ITD-positive patients appears to have a major impact on the prognostic relevance. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Heuser, L. M. Sly, B. Argiropoulos, F. Kuchenbauer, C. Lai, A. Weng, M. Leung, G. Lin, C. Brookes, S. Fung, et al. Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal Blood, November 5, 2009; 114(19): 3983 - 3993. [Abstract] [Full Text] [PDF] 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] F. P.G. Silva, I. Almeida, B. Morolli, G. 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