STANDARD_NAME TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP SYSTEMATIC_NAME M10184 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes up-regulated in monocytes 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 3 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 200702_s_at,200755_s_at,200807_s_at,200843_s_at,200875_s_at,200884_at,200951_s_at,200953_s_at,201037_at,201135_at,201215_at,201323_at,201334_s_at,201387_s_at,201417_at,201418_s_at,201427_s_at,201478_s_at,201563_at,201577_at,201606_s_at,201725_at,201798_s_at,201841_s_at,201906_s_at,201910_at,201920_at,201995_at,201998_at,202075_s_at,202077_at,202086_at,202145_at,202212_at,202234_s_at,202252_at,202270_at,202330_s_at,202353_s_at,202404_s_at,202609_at,202613_at,202667_s_at,203153_at,203236_s_at,203367_at,203382_s_at,203462_x_at,203549_s_at,203733_at,203735_x_at,203946_s_at,204033_at,204044_at,204073_s_at,204133_at,204326_x_at,204372_s_at,204401_at,204412_s_at,204439_at,204475_at,204521_at,204533_at,204584_at,204647_at,205020_s_at,205133_s_at,205417_s_at,205463_s_at,205483_s_at,205552_s_at,205680_at,205681_at,205738_s_at,205749_at,205909_at,205984_at,206206_at,206726_at,206932_at,207016_s_at,207335_x_at,207542_s_at,208029_s_at,208581_x_at,208614_s_at,208676_s_at,208688_x_at,208789_at,208799_at,208836_at,208891_at,208892_s_at,208896_at,209036_s_at,209100_at,209104_s_at,209122_at,209129_at,209160_at,209191_at,209210_s_at,209262_s_at,209278_s_at,209386_at,209387_s_at,209453_at,209478_at,209716_at,209900_s_at,209960_at,210004_at,210386_s_at,210511_s_at,210609_s_at,210749_x_at,210792_x_at,210976_s_at,211456_x_at,211535_s_at,211717_at,211936_at,211951_at,212012_at,212013_at,212173_at,212185_x_at,212226_s_at,212360_at,212479_s_at,212651_at,212680_x_at,212687_at,212761_at,212813_at,212816_s_at,212944_at,213129_s_at,213149_at,213164_at,213201_s_at,213205_s_at,213206_at,213236_at,213258_at,213338_at,213476_x_at,213524_s_at,213620_s_at,213634_s_at,213668_s_at,213720_s_at,213757_at,213793_s_at,214020_x_at,214038_at,214205_x_at,214214_s_at,214285_at,214453_s_at,214510_at,214661_s_at,214662_at,214794_at,214875_x_at,215034_s_at,215235_at,215404_x_at,215438_x_at,215722_s_at,215947_s_at,216977_x_at,217809_at,217824_at,217841_s_at,217942_at,217996_at,217997_at,218025_s_at,218099_at,218131_s_at,218145_at,218239_s_at,218289_s_at,218392_x_at,218418_s_at,218641_at,218670_at,218678_at,218723_s_at,218859_s_at,218950_at,219002_at,219098_at,219166_at,219211_at,219358_s_at,219434_at,219522_at,219648_at,219675_s_at,219799_s_at,219821_s_at,219863_at,219911_s_at,221005_s_at,221434_s_at,221506_s_at,221539_at,221577_x_at,221829_s_at,221923_s_at,221931_s_at,222010_at,222154_s_at,222206_s_at,222216_s_at,336_at,33767_at,45297_at GENE_SYMBOLS DDX24,CALU,HSPD1,EPRS1,NOP56,CKB,CCND2,CCND2,PFKP,ECHS1,PLS3,EBNA1BP2,ARHGEF12,UCHL1,SOX4,SOX4,SELENOP,DKC1,SORD,NME1,PWP1,CDC123,MYOF,HSPB1,CTDSPL,FARP1,SLC20A1,EXT1,ST6GAL1,PLTP,NDUFAB1,MX1,LY6E,PES1,SLC16A1,RAB13,GBP1,UNG,PSMD12,COL1A2,EPS8,CTPS1,SLC39A7,IFIT1,LGALS9,DUSP14,APOE,EIF3B,LPL,DEXI,PPFIBP1,ARG2,TRIP13,QPRT,MYRF,RRP9,MT1X,KHSRP,KCNN4,NEFH,IFI44L,MMP1,FAM216A,CXCL10,L1CAM,HOMER3,ARL4A,HSPE1,DAG1,PDGFA,ISG15,OAS1,MMP10,BCL2A1,FABP3,CYP1A1,POLE2,CRHBP,CD180,HPGDS,CH25H,ALDH1A2,ATP5ME,AQP1,LAPTM4B,MT1X,FLNB,PA2G4,EIF3B,CAVIN1,PSMB5,ATP1B3,DUSP6,DUSP6,DDX18,MDH2,IFRD2,NHP2,PLIN2,TRIP6,AKR1C3,TUBB6,FERMT2,NR2F6,TFPI2,TM4SF1,TM4SF1,SLC9A1,CENPX,CSF1,SLC16A1,HGF,OLR1,MTX1,INHBA,TP53I3,DDR1,SIVA1,PFKM,MT1H,FGFR1,ANKRD40,HSPA5,NOLC1,PXDN,PXDN,AK2,MT2A,PLPP3,AMPD2,RMND5A,RHOBTB1,PPP1R14B,LIMS1,TCF7L2,JAM3,CBS,SLC5A3,GCSH,DLAT,SLC5A3,TNNT1,RAD54L2,GOSR2,SASH1,TFPI,TMEM158,TUBB2A,G0S2,ICAM2,TRMU,SOX4,SMARCA4,GPS2,HOMER1,,CCL8,GLRX3,C1QBP,FABP3,IFI44,GPR20,NOP14,WDR43,PA2G4,APLP2,TM4SF1,SPTAN1,FGFR1,GSPT1,SNRPA1,FAM136A,SNRPA1,BZW2,UBE2J1,PPME1,MRPS35,NAP1L1,NAP1L1,ECI2,TEX2,GATAD2A,TRIB3,GTPBP4,UBA5,SFXN1,KANK2,ZFTA,PUS1,NES,RGCC,ESF1,ARAP3,FASTKD1,MYBBP1A,DNAAF2,USP18,ADAP2,TREM1,FJX1,MREG,UXS1,DHRS9,GFOD1,HERC5,SLCO4A1,PTDSS2,SLIRP,TNPO2,EIF4EBP1,GDF15,TNPO1,NPM1,SEH1L,TCP1,SPATS2L,NCLN,MRPL17,TBXA2R,NEFH,EHD2 FOUNDER_NAMES