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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3654-3661. Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-03-009233. This Article Full Text (PDF) All Versions of this Article: blood-2006-03-009233v1 108/12/3654    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 Meshinchi, S. Articles by Radich, J. P Search for Related Content PubMed PubMed Citation Articles by Meshinchi, S. Articles by Radich, J. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 31, 2006 Accepted July 24, 2006 Clinical implications of FLT3 mutations in pediatric AML Soheil Meshinchi*, Todd A Alonzo, Derek L Stirewalt, Michel Zwaan, Martin Zimmerman, Dirk Reinhardt, Gertjan JL Kaspers, Nyla A Heerema, Robert Gerbing, Beverly J Lange, and Jerald P Radich Fred Hutchinson Cancer Research Center, University of Washington Medical Center, Seattle, WA University of Southern California Keck School of Medicine, Los Angeles, CA Erasmus MC-Sophia Childrens Hospital, and Dutch Childhood Oncology Group, Rotterdam, Netherlands AML-BFM Study Group, Munster, Germany VU University Medical Center, and Dutch Childhood Oncology Group, Amsterdam, Netherlands The Ohio State University, Columbus, Ohio Children's Oncology Group, Arcadia, CA Childrens Hospital of Philadelphia, Philadelphia, PA Fred Hutchinson Cancer Research Institute, University of Washington Medical Center, Seattle, WA * Corresponding author; email: smeshinc{at}fhcrc.org. Activating mutations of the FLT3 gene occur due to an internal tandem duplication of the juxta-membrane domain (FLT3/ITD) or point mutation of the activation loop domain (FLT3/ALM). The presence of FLT3 mutations as well as the allelic ratio of FLT3/ITD (ITD-AR, mutant to wild type ratio)) may have prognostic significance. FLT3 mutation status of 630 children with de novo AML treated on CCG-2941/2961 was determined, and ITD-AR was determined for FLT3/ITD-positive patients. Clinical characteristics and outcomes for patients with FLT3/ALM, and FLT3/ITD at varying ITD-AR was determined and compared to those without FLT3 mutations (FLT3/WT). FLT3/ITD and FLT3/ALM were detected in 77 (12%) and 42 (6.7%) of the patients. Progression-free survival (PFS) was similar in patients with FLT3/ALM and FLT3/WT (51% vs. 55%, p=0.862). In contrast, PFS at 4 years from study entry for FLT3/ITD-positive patients was inferior to that of FLT3/WT patients (31% vs. 55%, p<0.001). PFS decreased with increasing FLT3/ITD-AR (p< 0.001), and those with ITD-AR >0.4 had a significantly worse PFS than those with lower ITD-AR (16% vs. 72%, p=0.001) or with FLT3/WT (55%, p<0.001). ITD-AR defines the prognostic significance in FLT3/ITD-positive AML and ITD-AR >0.4 is a significant, and independent prognostic factor for relapse in pediatric AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. P. Zarrinkar, R. N. Gunawardane, M. D. Cramer, M. F. Gardner, D. Brigham, B. Belli, M. W. Karaman, K. W. Pratz, G. Pallares, Q. Chao, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML) Blood, October 1, 2009; 114(14): 2984 - 2992. [Abstract] [Full Text] [PDF] S. Meshinchi and F. R. Appelbaum Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia Clin. Cancer Res., July 1, 2009; 15(13): 4263 - 4269. 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