STANDARD_NAME TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_3D_UP SYSTEMATIC_NAME M6670 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_3D_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes up-regulated in CD34+ [GeneID=947] hematopoetic cells by expression of NUP98-HOXA9 fusion [GeneID=4928;3205] off a retroviral vector at 3 days after transduction. DESCRIPTION_FULL NUP98-HOXA9, the chimeric protein resulting from the t(7;11)(p15;p15) chromosomal translocation, is a prototype of several NUP98 fusions that occur in myelodysplastic syndromes and acute myeloid leukemia. We examined its effect on differentiation, proliferation, and gene expression in primary human CD34+ hematopoietic cells. Colony-forming cell (CFC) assays in semisolid medium combined with morphologic examination and flow cytometric immunophenotyping revealed that NUP98-HOXA9 increased the numbers of erythroid precursors and impaired both myeloid and erythroid differentiation. In continuous liquid culture, cells transduced with NUP98-HOXA9 exhibited a biphasic growth curve with initial growth inhibition followed by enhanced long-term proliferation, suggesting an increase in the numbers of primitive self-renewing cells. This was confirmed by a dramatic increase in the numbers of long-term culture-initiating cells, the most primitive hematopoietic cells detectable in vitro. To understand the molecular mechanisms underlying the effects of NUP98-HOXA9 on hematopoietic cell proliferation and differentiation, oligonucleotide microarray analysis was done at several time points over 16 days, starting at 6 hours posttransduction. The early growth suppression was preceded by up-regulation of IFNbeta1 and accompanied by marked up-regulation of IFN-induced genes, peaking at 3 days posttransduction. In contrast, oncogenes such as homeobox transcription factors, FLT3, KIT, and WT1 peaked at 8 days or beyond, coinciding with increased proliferation. In addition, several putative tumor suppressors and genes associated with hematopoietic differentiation were repressed at later time points. These findings provide a comprehensive picture of the changes in proliferation, differentiation, and global gene expression that underlie the leukemic transformation of human hematopoietic cells by NUP98-HOXA9. PMID 16818636 GEOID AUTHORS Takeda A,Goolsby C,Yaseen NR CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1554524_a_at,1554526_at,1554712_a_at,1554997_a_at,1556643_at,1557113_at,1558105_a_at,1559663_at,1566482_at,1569540_at,1569652_at,200872_at,200887_s_at,200923_at,200986_at,201242_s_at,201243_s_at,201416_at,201418_s_at,201508_at,201601_x_at,201641_at,202086_at,202145_at,202180_s_at,202269_x_at,202270_at,202411_at,202458_at,202820_at,202869_at,202890_at,203065_s_at,203153_at,203304_at,203485_at,203569_s_at,203595_s_at,203882_at,204044_at,204069_at,204082_at,204187_at,204201_s_at,204211_x_at,204375_at,204415_at,204439_at,204529_s_at,204533_at,204546_at,204635_at,204747_at,204748_at,204774_at,204972_at,204994_at,205127_at,205483_s_at,205513_at,205552_s_at,205572_at,205609_at,205653_at,205660_at,205749_at,205844_at,205942_s_at,205984_at,206133_at,206298_at,206310_at,206332_s_at,206367_at,206446_s_at,206447_at,206828_at,206847_s_at,206932_at,206987_x_at,207017_at,207018_s_at,207077_at,207802_at,207836_s_at,208012_x_at,208392_x_at,208436_s_at,208557_at,208965_s_at,208966_x_at,209211_at,209212_s_at,209374_s_at,209417_s_at,209487_at,209488_s_at,209732_at,209757_s_at,209761_s_at,209762_x_at,209795_at,209859_at,209905_at,209969_s_at,210029_at,210145_at,210262_at,210375_at,210377_at,211029_x_at,211597_s_at,212224_at,212254_s_at,212592_at,212599_at,212614_at,212651_at,212820_at,212827_at,212944_at,213058_at,213164_at,213182_x_at,213293_s_at,213294_at,213348_at,213358_at,213541_s_at,213566_at,213668_s_at,213797_at,213844_at,213933_at,214022_s_at,214043_at,214059_at,214438_at,214453_s_at,214651_s_at,214716_at,215016_x_at,215071_s_at,215092_s_at,215146_s_at,215446_s_at,216894_x_at,217787_s_at,218400_at,218429_s_at,218501_at,218543_s_at,218943_s_at,218986_s_at,219209_at,219211_at,219235_s_at,219352_at,219534_x_at,219691_at,219737_s_at,219863_at,219874_at,219905_at,219932_at,221884_at,222793_at,223220_s_at,223434_at,223805_at,223991_s_at,224403_at,224558_s_at,224701_at,224806_at,224917_at,225239_at,225283_at,225344_at,225415_at,225636_at,225929_s_at,225931_s_at,225956_at,226145_s_at,226189_at,226279_at,226420_at,226550_at,226702_at,226756_at,226757_at,226853_at,227082_at,227195_at,227609_at,227725_at,227807_at,228152_s_at,228230_at,228233_at,228274_at,228507_at,228531_at,228617_at,228708_at,228904_at,229057_at,229199_at,229309_at,229350_x_at,229450_at,229461_x_at,229521_at,229530_at,229638_at,230000_at,230036_at,230405_at,231109_at,231175_at,231382_at,231577_s_at,231947_at,231956_at,232098_at,232375_at,234989_at,235046_at,235072_s_at,235157_at,235521_at,235643_at,235737_at,235753_at,235884_at,236034_at,236300_at,236395_at,236738_at,236892_s_at,237009_at,237261_at,238669_at,238732_at,238919_at,239218_at,239979_at,241379_at,241751_at,241837_at,241916_at,241926_s_at,242002_at,242234_at,242414_at,242476_at,242625_at,242920_at,242961_x_at,243271_at,244503_at,244625_at,244845_at,32128_at,37170_at,44783_s_at,53720_at,AFFX-HUMISGF3A/M97935_3_at,AFFX-HUMISGF3A/M97935_5_at,AFFX-HUMISGF3A/M97935_MA_at,AFFX-HUMISGF3A/M97935_MB_at GENE_SYMBOLS OLFM3,OLFM3,GLYATL2,PTGS2,BISPR,RPS6KA5,SLC9A7,,,,MLLT3,S100A10,STAT1,LGALS3BP,SERPING1,ATP1B1,ATP1B1,SOX4,SOX4,IGFBP4,IFITM1,BST2,MX1,LY6E,MVP,GBP1,GBP1,IFI27,PRSS23,AHR,OAS1,MAP7,CAV1,IFIT1,BAMBI,RTN1,OFD1,IFIT5,IRF9,QPRT,MEIS1,PBX3,GMPR,PTPN13,EIF2AK2,CLSTN3,IFI6,IFI44L,TOX,CXCL10,KIAA0513,RPS6KA5,IFIT3,PTGS2,EVI2A,OAS2,MX2,PTGS1,ISG15,TCN1,OAS1,ANGPT2,ANGPT1,CTSG,OASL,CYP1A1,VNN1,ACSM3,CRHBP,XAF1,ARHGAP22,SPINK2,IFI16,REN,CELA2B,CELA2B,TXK,HOXA7,CH25H,FGF18,RAB27B,RAB27B,CELA2B,CRISP3,RBPMS,SP110,SP110,IRF7,HOXA6,IFI16,IFI16,KLF5,KLF5,IGHM,IFI35,RBPMS,RBPMS,CLEC2B,MYCN,SP110,SP110,CD69,TRIM9,HOXA9,STAT1,IDO1,PLA2G4A,CRISP2,PTGER3,ACSM3,FGF18,HOPX,ALDH1A1,DST,JCHAIN,AUTS2,ARID5B,RHOBTB1,DMXL2,IGHM,SLC5A3,TTC28,SLC5A3,CDKN1C,TRIM22,EIF2AK2,CDKN1C,MTCL1,ERG,RNASE6,SOX4,RSAD2,HOXA5,PTGER3,IFITM1,PTPRD,IFI44,HLX,IFI44,HOXA9,BMP2K,DST,H2AC6,NFAT5,TTC28,LOX,CDKN1C,GALNT2,OAS3,SHFL,ARHGEF3,PARP12,RIGI,DDX60,IFIH1,USP18,PHACTR4,HERC6,CDKN1C,SAMD9,PCDH9,HERC5,SLC12A8,ERMAP,SLC27A6,MECOM,RIGI,PARP9,GBP3,OSBPL6,GALNT2,FCRL4,MALAT1,PARP14,TRIM25,VMP1,NEAT1,ARRDC4,NCOA7,DTX3L,STAT2,RNF213,RNF213,CREBRF,FRAS1,ITGB8,PRSS23,MECOM,SLC9A7,CMPK2,CCDC71L,IFIT2,BMP2K,ZBTB20,ZNF503,EPSTI1,ST6GALNAC1,PARP9,DDX60L,HELZ2,FREM1,SDSL,PDE3A,SAMD9,XAF1,RAB27B,HOXB3,SCN2A,SCN9A,ADRB1,PARP10,IFIT3,NEGR1,CCDC71L,GUCY1A1,IRX3,RNF213,SAMD9L,IRF1-AS1,,BEND6,FGF18,GBP1,MYCT1,RNF213,DST,STAT1,NEAT1,INPP4B,KIF13A,,HOXA3,SAMD9L,TSLP,HOXA7,LINC02604,ANGPT2,PDE3A,,C3orf80,HOXB-AS3,,ANGPT2,PTGS1,COL24A1,PCDH9,PDE1C,,APLF,OFD1,,,ERG,NKAIN2,XAF1,QPRT,,RSAD2,,RIGI,,,,,CCL18,BMP2K,HEY1,SHFL,STAT1,STAT1,STAT1,STAT1 FOUNDER_NAMES