STANDARD_NAME VALK_AML_CLUSTER_10 SYSTEMATIC_NAME M18784 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VALK_AML_CLUSTER_10 NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Top 40 genes from cluster 10 of acute myeloid leukemia (AML) expression profile; 41% of the samples are FAB M1 subtype, 45% have up-regulated EVI1 [GeneID=2122] expression; indicate poor survival. DESCRIPTION_FULL 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. PMID 15084694 GEOID 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 CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Supplementary Table J1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 200671_s_at,200672_x_at,202551_s_at,203756_at,203796_s_at,204004_at,204083_s_at,204484_at,204540_at,204581_at,204917_s_at,205330_at,205382_s_at,205933_at,206111_at,207788_s_at,207836_s_at,208614_s_at,209282_at,209436_at,209437_s_at,209487_at,209488_s_at,209576_at,209679_s_at,209763_at,209906_at,212071_s_at,212558_at,212750_at,212827_at,213488_at,213506_at,214575_s_at,218086_at,218899_s_at,219145_at,220377_at,41577_at,47560_at GENE_SYMBOLS SPTBN1,SPTBN1,CRIM1,ARHGEF17,BCL7A,PAWR,TPM2,PIK3C2B,EEF1A2,CD22,MLLT3,MN1,CFD,SETBP1,RNASE2,SORBS3,RBPMS,FLNB,PRKD2,SPON1,SPON1,RBPMS,RBPMS,GNAI1,SMAGP,CHRDL1,C3AR1,SPTBN1,SPRY1,PPP1R16B,IGHM,SNED1,F2RL1,AZU1,NPDC1,BAALC,ADGRL1,FAM30A,PPP1R16B,ADGRL1 FOUNDER_NAMES