STANDARD_NAME	MULLIGHAN_NPM1_SIGNATURE_3_UP
SYSTEMATIC_NAME	M10277
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MULLIGHAN_NPM1_SIGNATURE_3_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	The 'NPM1 signature 3': genes up-regulated in pediatric AML (acute myeloid leukemia) with mutated NPM1 [GeneID=4869] compared to the AML cases with intact NPM1 and MLL [GeneID=4297].
DESCRIPTION_FULL	Somatic mutations in nucleophosmin (NPM1) occur in approximately 35% of adult acute myeloid leukemia (AML). To assess the frequency of NPM1 mutations in pediatric AML, we sequenced NPM1 in the diagnostic blasts from 93 pediatric AML patients. Six cases harbored NPM1 mutations, with each case lacking common cytogenetic abnormalities. To explore the phenotype of the AMLs with NPM1 mutations, gene expression profiles were obtained using Affymetrix U133A microarrays. NPM1 mutations were associated with increased expression of multiple homeobox genes including HOXA9, A10, B2, B6 and MEIS1. As dysregulated homeobox gene expression is also a feature of MLL-rearranged leukemia, the gene expression signatures of NPM1-mutated and MLL-rearranged leukemias were compared. Significant differences were identified between these leukemia subtypes including the expression of different HOX genes, with NPM1-mutated AML showing higher levels of expression of HOXB2, B3, B6 and D4. These results confirm recent reports of perturbed HOX expression in NPM1-mutated adult AML, and provide the first evidence that the NPM1-mutated signature is distinct from MLL-rearranged AML. These findings suggest that mutated NPM1 leads to dysregulated HOX expression via a different mechanism than MLL rearrangement.
PMID	17597811
GEOID	
AUTHORS	Mullighan CG,Kennedy A,Zhou X,Radtke I,Phillips LA,Shurtleff SA,Downing JR
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 7S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200827_at,201008_s_at,201009_s_at,201086_x_at,201146_at,201185_at,201200_at,201218_at,201227_s_at,201228_s_at,201229_s_at,201395_at,201413_at,201427_s_at,201432_at,201451_x_at,201625_s_at,201663_s_at,201664_at,201828_x_at,201834_at,201845_s_at,201851_at,201859_at,202085_at,202190_at,202272_s_at,202297_s_at,202346_at,202377_at,202399_s_at,202403_s_at,202500_at,202533_s_at,202537_s_at,202767_at,202913_at,202940_at,203017_s_at,203035_s_at,203291_at,203302_at,203327_at,203512_at,203517_at,203567_s_at,203568_s_at,203589_s_at,203610_s_at,203741_s_at,203747_at,203759_at,203805_s_at,203836_s_at,203837_at,203955_at,203963_at,203971_at,204021_s_at,204030_s_at,204069_at,204072_s_at,204074_s_at,204082_at,204099_at,204113_at,204137_at,204180_s_at,204202_at,204260_at,204315_s_at,204399_s_at,204461_x_at,204479_at,204492_at,204571_x_at,204647_at,204742_s_at,204832_s_at,204884_s_at,204943_at,204970_s_at,204995_at,204998_s_at,205017_s_at,205023_at,205116_at,205120_s_at,205171_at,205264_at,205305_at,205317_s_at,205346_at,205366_s_at,205395_s_at,205435_s_at,205453_at,205522_at,205558_at,205566_at,205600_x_at,205669_at,205695_at,205753_at,205804_s_at,205867_at,205967_at,205968_at,205977_s_at,205990_s_at,206003_at,206110_at,206111_at,206138_s_at,206289_at,206310_at,206389_s_at,206395_at,206441_s_at,206652_at,206837_at,206847_s_at,206853_s_at,207023_x_at,207050_at,207071_s_at,207108_s_at,207198_s_at,207209_at,207231_at,207250_at,207374_at,207392_x_at,207503_at,207504_at,207616_s_at,207634_at,207761_s_at,207830_s_at,207910_at,207983_s_at,208040_s_at,208091_s_at,208143_s_at,208146_s_at,208154_at,208196_x_at,208212_s_at,208345_s_at,208393_s_at,208414_s_at,208442_s_at,208447_s_at,208557_at,208604_s_at,208648_at,208715_at,208716_s_at,208813_at,208900_s_at,208958_at,208963_x_at,208967_s_at,208996_s_at,208999_at,209006_s_at,209019_s_at,209248_at,209370_s_at,209375_at,209451_at,209479_at,209605_at,209653_at,209697_at,209753_s_at,209905_at,209912_s_at,209930_s_at,209931_s_at,209990_s_at,210110_x_at,210145_at,210184_at,210211_s_at,210282_at,210379_s_at,210437_at,210447_at,210540_s_at,210548_at,210549_s_at,210662_at,210867_at,210947_s_at,210969_at,211022_s_at,211169_s_at,211189_x_at,211326_x_at,211352_s_at,211424_x_at,211425_x_at,211439_at,211446_at,211523_at,211525_s_at,211570_s_at,211585_at,211606_at,211659_at,211769_x_at,211804_s_at,211833_s_at,211922_s_at,211969_at,212028_at,212129_at,212174_at,212175_s_at,212314_at,212374_at,212412_at,212439_at,212530_at,212638_s_at,212756_s_at,212800_at,212809_at,212851_at,213110_s_at,213123_at,213147_at,213150_at,213168_at,213169_at,213358_at,213384_x_at,213436_at,213623_at,213648_at,213844_at,213899_at,214187_x_at,214299_at,214376_at,214425_at,214457_at,214486_x_at,214494_s_at,214564_s_at,214651_s_at,214656_x_at,214719_at,214747_at,214804_at,214938_x_at,215064_at,215143_at,215171_s_at,215237_at,215419_at,215444_s_at,215525_at,215555_at,215556_at,215570_s_at,215573_at,215605_at,215629_s_at,215801_at,215823_x_at,215841_at,215881_x_at,216005_at,216198_at,216216_at,216304_x_at,216417_x_at,216459_x_at,216492_at,216506_x_at,216529_at,216612_x_at,216679_at,216803_at,216872_at,216877_at,216969_s_at,217127_at,217167_x_at,217188_s_at,217307_at,217353_at,217371_s_at,217517_x_at,217650_x_at,217717_s_at,217778_at,217853_at,217963_s_at,217975_at,218119_at,218230_at,218242_s_at,218257_s_at,218326_s_at,218404_at,218446_s_at,218456_at,218466_at,218477_at,218480_at,218614_at,218639_s_at,218656_s_at,218695_at,218711_s_at,218813_s_at,218847_at,218857_s_at,218886_at,218916_at,218942_at,219007_at,219105_x_at,219195_at,219203_at,219229_at,219231_at,219246_s_at,219254_at,219304_s_at,219322_s_at,219340_s_at,219376_at,219412_at,219452_at,219454_at,219502_at,219507_at,219598_s_at,219621_at,219893_at,219999_at,220033_at,220154_at,220162_s_at,220226_at,220326_s_at,220336_s_at,220466_at,220529_at,220572_at,220608_s_at,220665_at,220694_at,220798_x_at,220841_s_at,220856_x_at,220874_at,221064_s_at,221164_x_at,221244_s_at,221294_at,221347_at,221354_s_at,221443_x_at,221473_x_at,221606_s_at,221631_at,221685_s_at,221702_s_at,221737_at,221771_s_at,221813_at,221823_at,221883_at,221904_at,222170_at,222319_at,222338_x_at,33494_at,34408_at,38918_at,40359_at,57540_at,87100_at
GENE_SYMBOLS	PLOD1,TXNIP,TXNIP,SON,NFE2L2,HTRA1,CREG1,,NDUFB8,ARIH2,ARIH2,RBM5,HSD17B4,SELENOP,CAT,LINC02637,INSIG1,SMC4,SMC4,RTL8C,PRKAB1,RYBP,SH3GL1,SRGN,TJP2,CSTF1,FBXO28,RER1,UBE2K,LEPROT,AP3S2,COL1A2,DNAJB2,DHFR,CHMP2B,ACP2,ARHGEF11,WNK1,SSX2IP,PIAS3,CNOT4,DCK,IDE,TRAPPC3,MTX2,TRIM38,TRIM38,TFDP2,TRIM38,ADCY7,AQP3,ST3GAL4,FANCA,MAP3K5,MAP3K5,PPP1R26,CA12,SLC31A1,PURA,SCHIP1,MEIS1,FRY,CEP104,PBX3,SMARCD3,CELF1,GPR137B,ZBTB43,IQCE,CHGB,GTSE1,EML2,RAD1,OSTF1,ARHGAP11A,PIN4,HOMER3,PDS5B,BMPR1A,HUS1,ADAM12,MAFG,CDK5R1,ATF5,MBNL2,RAD51,LAMA2,SGCB,PTPN4,POLR1G,FGL1,SLC15A2,ST3GAL2,HOXB6,MRE11,AAK1,HOXB2,,TRAF6,ABHD2,HOXB5,NCAM2,SDS,CRP,TRAF3IP3,PTPN11,H4C3,KCNS3,EPHA1,WNT5A,CEP135,H3C10,RNASE2,PI4KB,HOXA4,SPINK2,PDE3A,DGKG,COMMD4,ZMYM5,ALX1,HOXA7,MAP3K7,KRT10,CACNA2D1,ACO1,NIPBL,LIMS1,CETN1,DZIP3,SIX6,PLSCR2,UGT2B15,TCP10L3,CA7,TANK,PDCD1,TMT1A,PPP1R8,SCGB1D1,STAG2,MYBPC3,VOPP1,EDDM3A,CPVL,,NFATC1,ALK,POU3F1,RAD50,HOXB3,ATM,PRPS1,HOXA6,HOXA3,VCP,TMCO1,TMCO1,GOT1,TOP1,ERP44,FADS1,AK2,POLR2C,SEPTIN8,RSRP1,PINK1,GHITM,SH3BP2,XPC,TANK,CCDC28A,TST,KPNA4,,TMPO,HOXA9,AP5Z1,NFE2,FKBP1B,GABBR2,HNRNPH3,PLA2G4A,ITGAX,HSP90AA1,ZMYM2,TLK1,MAGEA9,GLUD2,B4GALT4,CCL23,CCL23,KYNU,CNOT4,MSH3,PKN2,ATRX,PPP1R3A,CD84,HFE,NCOA3,,SSX4,,RGSL1,GNRHR,GP5,RAPSN,,,GPR135,SERINC3,CDK2,BAX,CAT,HSP90AA1,RBM25,,AK2,AK2,SEL1L3,FEM1B,PDLIM5,IP6K1,NEK7,WWP1,UBR2,STX6,NFATC2IP,DCUN1D4,COL4A5,MFAP3,HOXA10,HOXA10,SP3,SEMA5A,MTCL1,PLCB3,CNR1,KIF3A,EXOSC7,HOXA5,METAP2,,TOP3A,MAPK10,,HOXA2,CFLAR,SPG7,PCDHGC3,HOXA9,MYO1C,SLC46A3,ZBED4,CENPI,HMGB1,SC5D,DPY19L2P2,TIMM17A,DOCK9,ZFR2,TRIM31,,,,ZNF780B,,,DLEU2,,PABPC1P3,GUCA1B,SSX2,TNC,,SLIT3,YME1L1,HOXB9,DDR1-DT,,MLLT10,,,,,,,KIF22,CTH,GK,ERG28,,HNRNPA1P37,IL15,,ST3GAL2,YWHAB,SLC39A1,TNS3,BEX3,TCEAL9,TIMM23,ARFIP1,KMT5B,UGGT1,LGR4,SNX10,TVP23B,CAPRIN2,TBC1D17,TMEM14A,AGBL5,RESF1,ZXDC,LHFPL6,EXOSC4,CAVIN2,SH3GLB2,IGF2BP2,ASRGL1,PAK1IP1,ZNF768,PIP4K2C,NUP43,ORC6,PPARGC1A,EMC9,SLCO3A1,TGS1,ARL6IP4,OGFOD3,PDGFD,WRAP73,CLN8,ZNF322,RAB38,DPEP2,EGFL6,NEIL3,RSRC1,RWDD1,,CCDC71,MAN2A2,CYB5RL,DST,CARD9,TRPM8,ARHGEF40,GP6,CCDC15,,ANKRD42-DT,,LUZP4,,PLPPR3,AHI1,,,UNKL,CHST5,,GPR21,CHRM5,MCHR1,PRLH,SERINC3,HMGN5,CACNA1I,SPDL1,TM2D3,GNA12,MPHOSPH8,FBXO42,MACIR,PKNOX1,FAM131A,ZNF213-AS1,,APTX,ETFDH,RTN2,SOX13,RASSF7,RBKS,ABHD2
FOUNDER_NAMES