STANDARD_NAME TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP SYSTEMATIC_NAME M12085 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes up-regulated by RUNX1-RUNX1T1 [GeneID=861;862] fusion protein in normal hematopoietic progenitors; their expression was sustained in subsequently developing erythroid lineage. DESCRIPTION_FULL The t(8;21)(q22;q22) occurs frequently in acute myelogenous leukaemia and gives rise to the transcription factor fusion protein, RUNX1-RUNX1T1 (also known as AML1-ETO). To identify the genes dysregulated by the aberrant transcriptional activity of RUNX1-RUNX1T1, we used microarrays to determine the effect of this mutation on gene expression in human progenitor cells and during subsequent development. Gene signatures of these developmental subsets were very dissimilar indicating that effects of RUNX1-RUNX1T1 are highly context dependent. We focused on gene changes associated with the granulocytic lineage and identified a clinically relevant subset of these by comparison with 235 leukaemia patient transcriptional signatures. We confirmed the overexpression of a number of significant genes (Sox4, IL-17BR, CD200 and gamma-catenin). Further, we show that overexpression of CD200 and gamma-catenin is also associated with the inv(16) abnormality which like RUNX1-RUNX1T1 disrupts core binding factor activity. We investigated the functional significance of CD200 and gamma-catenin overexpression in normal human progenitor cells. The effect of IL17 on growth was also assessed. Individually, none of these changes were sufficient to recapitulate the effects of RUNX1-RUNX1T1 on normal development. These data provide the most comprehensive and pertinent assessment of the effect of RUNX1-RUNX1T1 on gene expression and demonstrate the highly context-dependent effects of this fusion gene. PMID 17898786 GEOID E-MEXP-583 AUTHORS Tonks A,Pearn L,Musson M,Gilkes A,Mills KI,Burnett AK,Darley RL CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 5S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 201324_at,201325_s_at,201387_s_at,201416_at,201417_at,201467_s_at,201468_s_at,201590_x_at,201841_s_at,201860_s_at,201963_at,202748_at,203404_at,203739_at,204044_at,204088_at,204105_s_at,204647_at,205749_at,205984_at,206291_at,206332_s_at,206932_at,207016_s_at,207857_at,208779_x_at,208891_at,208892_s_at,208893_s_at,208937_s_at,208961_s_at,209034_at,209365_s_at,209373_at,209386_at,209387_s_at,209487_at,209583_s_at,209967_s_at,210427_x_at,211100_x_at,211102_s_at,212657_s_at,213503_x_at,213541_s_at,213627_at,215034_s_at,215489_x_at,216035_x_at,217678_at,217996_at,217997_at,219255_x_at,220532_s_at,221577_x_at,221731_x_at,222108_at GENE_SYMBOLS EMP1,EMP1,UCHL1,SOX4,SOX4,NQO1,NQO1,ANXA2,HSPB1,PLAT,ACSL1,GBP2,ARMCX2,ZNF217,QPRT,P2RX4,NRCAM,HOMER3,CYP1A1,CRHBP,NTS,IFI16,CH25H,ALDH1A2,LILRA2,DDR1,DUSP6,DUSP6,DUSP6,ID1,KLF6,PNRC1,ECM1,MALL,TM4SF1,TM4SF1,RBPMS,CD200,CREM,ANXA2,LILRA2,LILRA2,IL1RN,ANXA2,ERG,MAGED2,TM4SF1,HOMER3,TCF7L2,SLC7A11,NAP1L1,NAP1L1,IL17RB,TMEM176B,GDF15,VCAN,AMIGO2 FOUNDER_NAMES