An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML BLOOD Bullinger, L., Doehner, K., Kranz, R., Stirner, C., Froeling, S., Scholl, C., Kim, Y. H., Schlenk, R. F., Tibshirani, R., Doehner, H., Pollack, J. R. 2008; 111 (9): 4490-4495


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.

View details for DOI 10.1182/blood-2007-09-115055

View details for Web of Science ID 000255387400016

View details for PubMedID 18309032