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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4490-4495. Prepublished online as a Blood First Edition Paper on February 28, 2008; DOI 10.1182/blood-2007-09-115055. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-115055v1 111/9/4490    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 Bullinger, L. Articles by Pollack, J. R. Search for Related Content PubMed PubMed Citation Articles by Bullinger, L. Articles by Pollack, J. R. Related Collections Neoplasia Gene Expression Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML Lars Bullinger1, Konstanze Döhner1, Raphael Kranz1, Christoph Stirner1, Stefan Fröhling1, Claudia Scholl1, Young H. Kim2, Richard F. Schlenk1, Robert Tibshirani3, Hartmut Döhner1,*, and Jonathan R. Pollack2,* 1 Department of Internal Medicine III, University of Ulm, Ulm, Germany; and Departments of2 Pathology and 3 Statistics and Health Research & Policy, Stanford University, CA Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3-ITD mutation and to evaluate the utility of a FLT3 signature for prognostication. DNA microarrays were used to profile gene expression in a training set of 65 NK-AML cases, and supervised analysis, using the Prediction Analysis of Microarrays method, was applied to build a gene expression–based predictor of FLT3-ITD mutation status. The optimal predictor, composed of 20 genes, was then evaluated by classifying expression profiles from an independent test set of 72 NK-AML cases. The predictor exhibited modest performance (73% sensitivity; 85% specificity) in classifying FLT3-ITD status. Remarkably, however, the signature outperformed FLT3-ITD mutation status in predicting clinical outcome. The signature may better define clinically relevant FLT3 signaling and/or alternative changes that phenocopy FLT3-ITD, whereas the signature genes provide a starting point to dissect these pathways. Our findings support the potential clinical utility of a gene expression–based measure of FLT3 pathway activation in AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Bacher, A. Kohlmann, and T. Haferlach Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies Brief Funct Genomic Proteomic, May 27, 2009; (2009) elp011v1. [Abstract] [Full Text] [PDF] B. J. Wouters, B. Lowenberg, and R. Delwel A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects Blood, January 8, 2009; 113(2): 291 - 298. [Abstract] [Full Text] [PDF] K. H. Metzeler, M. Hummel, C. D. Bloomfield, K. Spiekermann, J. Braess, M.-C. Sauerland, A. Heinecke, M. Radmacher, G. Marcucci, S. P. Whitman, et al. An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia Blood, November 15, 2008; 112(10): 4193 - 4201. [Abstract] [Full Text] [PDF] Stratifying Risk in AML Journal Watch Oncology and Hematology, May 13, 2008; 2008(513): 1 - 1. [Full Text]

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