STANDARD_NAME	TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_3D_DN
SYSTEMATIC_NAME	M3210
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_3D_DN
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes down-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	1553723_at,1555339_at,1555340_x_at,1555355_a_at,1555600_s_at,201506_at,202917_s_at,203535_at,204446_s_at,204681_s_at,205266_at,205919_at,206682_at,207691_x_at,208075_s_at,209147_s_at,209960_at,210889_s_at,210992_x_at,211298_s_at,213238_at,214146_s_at,214366_s_at,214637_at,214974_x_at,215049_x_at,215101_s_at,218559_s_at,220811_at,224799_at,224833_at,226218_at,230170_at,232760_at,233737_s_at,235438_at,242281_at
GENE_SYMBOLS	ADGRG3,,,ETS1,APOL4,TGFBI,S100A8,S100A9,ALOX5,RAPGEF5,LIF,HBE1,CLEC10A,ENTPD1,CCL7,PLPP1,HGF,FCGR2B,FCGR2A,ALB,ATP10D,PPBP,ALOX5,,CXCL5,CD163,CXCL5,MAFB,PRG3,NDFIP2,ETS1,IL7R,OSM,TEX15,LINC02806,CYP7B1,GLUL
FOUNDER_NAMES