Human Gene Set: VALK_AML_CLUSTER_4


Standard name VALK_AML_CLUSTER_4
Systematic name M4253
Brief description Top 40 genes from cluster 4 of acute myeloid leukemia (AML) expression profile; 87% of the samples are FAB M1 subtype, 53% bear mutations in CEBPA [GeneID=1050].
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15084694   Authors: Valk PJ,Verhaak RG,Beijen MA,Erpelinck CA,Barjesteh van Waalwijk van Doorn-Khosrovani S,Boer JM,Beverloo HB,Moorhouse MJ,van der Spek PJ,Löwenberg B,Delwel R
Exact source Supplementary Table D1
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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