STANDARD_NAME	TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_GRANULOCYTE_UP
SYSTEMATIC_NAME	M4661
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_GRANULOCYTE_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in granulocytes by RUNX1-RUNX1T1 [GeneID=861;862] fusion.
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 2S: list 2
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	201015_s_at,201416_at,201417_at,201418_s_at,201564_s_at,201737_s_at,201841_s_at,202145_at,203037_s_at,203373_at,203608_at,203989_x_at,204069_at,204073_s_at,204468_s_at,204807_at,205133_s_at,205608_s_at,205609_at,205749_at,205984_at,206283_s_at,207143_at,207199_at,207550_at,207968_s_at,208541_x_at,208937_s_at,208965_s_at,209199_s_at,209386_at,209387_s_at,209576_at,209583_s_at,210299_s_at,212224_at,212384_at,212614_at,212813_at,213194_at,213506_at,213826_s_at,214452_at,215222_x_at,215977_x_at,218033_s_at,218345_at,218418_s_at,219166_at,219255_x_at,219354_at,219789_at,219855_at,220532_s_at,221618_s_at,221884_at,221918_at,221942_s_at,222240_s_at,33767_at
GENE_SYMBOLS	JUP,SOX4,SOX4,SOX4,FSCN1,MARCHF6,HSPB1,LY6E,MTSS1,SOCS2,ALDH5A1,F2R,MEIS1,MYRF,TIE1,RXYLT1,HSPE1,ANGPT1,ANGPT1,CYP1A1,CRHBP,TAL1,CDK6,TERT,MPL,MEF2C,TFAM,ID1,IFI16,MEF2C,TM4SF1,TM4SF1,GNAI1,CD200,FHL1,ALDH1A1,DDX39B,ARID5B,JAM3,ROBO1,F2RL1,,BCAT1,MACF1,GK,SNN,TMEM176A,KANK2,DNAAF2,IL17RB,KLHL26,NPR3,NUDT11,TMEM176B,TAF9B,MECOM,CDK17,GUCY1A1,ISYNA1,NEFH
FOUNDER_NAMES