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Previous Volume 350:1617-1628 April 15, 2004 Number 16 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Liu, E. T. Editorial by Grimwade, D. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. However, this combined approach provides correct therapeutic and prognostic information in only 50 percent of cases.

Methods We determined the gene-expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML using Affymetrix U133A GeneChips containing approximately 13,000 unique genes or expression-signature tags. Data analyses were carried out with Omniviz, significance analysis of microarrays, and prediction analysis of microarrays software. Statistical analyses were performed to determine the prognostic significance of cases of AML with specific molecular signatures.

Results Unsupervised cluster analyses identified 16 groups of patients with AML on the basis of molecular signatures. We identified the genes that defined these clusters and determined the minimal numbers of genes needed to identify prognostically important clusters with a high degree of accuracy. The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations (CEBPA), and abnormal oncogene expression (EVI1). We identified several novel clusters, some consisting of specimens with normal karyotypes. A unique cluster with a distinctive gene-expression signature included cases of AML with a poor treatment outcome.

Conclusions Gene-expression profiling allows a comprehensive classification of AML that includes previously identified genetically defined subgroups and a novel cluster with an adverse prognosis.

Source Information

From the Departments of Hematology (P.J.M.V., R.G.W.V., M.A.B., C.A.J.E., S.B.W.D.-K., B.L., R.D.), Clinical Genetics (H.B.B.), and Bioinformatics (M.J.M., P.J.S.), Erasmus University Medical Center, Rotterdam; and the Leiden Genome Technology Center and the Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden (J.M.B.) — both in the Netherlands.

Address reprint requests to Dr. Valk at Erasmus University Medical Center Rotterdam, Department of Hematology, Ee13, Dr. Molewaterplein 50, 3015 GE Rotterdam Z-H, the Netherlands, or at p.valk{at}erasmusmc.nl.

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