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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2002-12-3627. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3627v1 102/7/2387    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 Zwaan, C. M. Articles by Griesinger, F. Search for Related Content PubMed PubMed Citation Articles by Zwaan, C. M. Articles by Griesinger, F. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2003, Vol. 102, No. 7, pp. 2387-2394 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance Christian M. Zwaan, Soheil Meshinchi, Jerald P. Radich, Anjo J. P. Veerman, Dieuwke R. Huismans, Leonhard Munske, Martina Podleschny, Karel Hählen, Rob Pieters, Martin Zimmermann, Dirk Reinhardt, Jochen Harbott, Ursula Creutzig, Gertjan J. L. Kaspers, and Frank Griesinger From the Department of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, the Netherlands; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Hematology and Oncology, University of Göttingen, Germany; Dutch Childhood Oncology Group, The Hague, the Netherlands; Department of Pediatric Oncology, Sophia Children's Hospital, Rotterdam, the Netherlands; Acute Myeloid Leukemia-Berlin-Frankfurt-Münster Study Group, Münster, Germany; and Oncogenetic Laboratory, Children's Hospital, Giessen, Germany. FLT3 is a receptor tyrosine kinase involved in the proliferation and differentiation of hematopoietic stem cells. FLT3 internal tandem duplications (FLT3/ITDs) are reported in acute myeloid leukemia (AML) and predict poor clinical outcome. We found FLT3/ITDs in 11.5% of 234 children with de novo AML. FLT3/ITD-positive patients were significantly older and had higher percentages of normal cytogenetic findings or French-American-British (FAB) classification M1/M2 and lower percentages of 11q23 abnormalities or FAB M5. FLT3/ITD-positive patients had lower remission induction rates (70% vs 88%; P = .01) and lower 5-year probability rates of event-free survival (pEF) (29% vs 46%; P = .0046) and overall survival (32% vs 58%; P = .037). Patients with high ratios (higher than the median) between mutant and wild-type FLT3 had significantly worse 2-year EFS rates than FLT3/ITD-negative patients (pEFS 20% vs 61%; P = .037), whereas patients with ratios lower than the median did not (pEFS 44% vs 61%; P = .26). FLT3/ITD was the strongest independent predictor for pEFS, with an increase in relative risk for an event of 1.92 (P = .01). Using an MTT (methyl-thiazol-tetrazolium)-based assay, we studied cellular drug resistance on 15 FLT3/ITD-positive and 125 FLT3/ITD-negative AML samples, but we found no differences in cellular drug resistance that could explain the poor outcomes in FLT3/ITD-positive patients. We conclude that FLT3/ITD is less common in pediatric than in adult AML. FLT3/ITD is a strong and independent adverse prognostic factor, and high ratios between mutant and WT-FLT3 further compromise prognosis. However, poor outcomes in FLT3/ITD-positive patients could not be attributed to increased in vitro cellular drug resistance. (Blood. 2003;102:2387-2394) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Meshinchi, D. L. Stirewalt, T. A. Alonzo, T. J. Boggon, R. B. Gerbing, J. L. Rocnik, B. J. Lange, D. G. Gilliland, and J. P. 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