Prognostically useful gene-expression profiles in acute myeloid leukemia

被引:1073
作者
Valk, PJM
Verhaak, RGW
Beijen, MA
Erpelinck, CAJ
van Doorn-Khosrovani, SBV
Boer, JM
Beverloo, HB
Moorhouse, MJ
van der Spek, PJ
Löwenberg, B
Delwel, R
机构
[1] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam ZH, Netherlands
[2] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3015 GE Rotterdam ZH, Netherlands
[3] Erasmus Univ, Med Ctr, Dept Bioinformat, NL-3015 GE Rotterdam ZH, Netherlands
[4] Leiden Univ, Med Ctr, Leiden Genome Technol Ctr, Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands
关键词
D O I
10.1056/NEJMoa040465
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:1617 / 1628
页数:12
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