STANDARD_NAME	HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN
SYSTEMATIC_NAME	M12153
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes down-regulated in bone marrow hematopoietic stem cells (HSC, CD34+ [GeneID=947]) from patients with high risk of myelodysplastic syndrom (MDS) compared to the low risk patients.
DESCRIPTION_FULL	Gene patterns of expression in purified CD34(+) bone marrow cells from 7 patients with low-risk myelodysplastic syndrome (MDS) and 4 patients with high-risk MDS were compared with expression data from CD34(+) bone marrow cells from 4 healthy control subjects. CD34(+) cells were isolated by magnetic cell separation, and high-density oligonucleotide microarray analysis was performed. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction. Class membership prediction analysis selected 11 genes. Using the expression profile of these genes, we were able to discriminate patients with low-risk from patients with high-risk MDS and both patient groups from the control group by hierarchical clustering (Spearman confidence). The power of these 11 genes was verified by applying the algorithm to an unknown test set containing expression data from 8 additional patients with MDS (3 at low risk, 5 at high risk). Patients at low risk could be distinguished from those at high risk by clustering analysis. In low-risk MDS, we found that the retinoic-acid-induced gene (RAI3), the radiation-inducible, immediate-early response gene (IEX1), and the stress-induced phosphoprotein 1 (STIP1) were down-regulated. These data suggest that CD34(+) cells from patients with low-risk MDS lack defensive proteins, resulting in their susceptibility to cell damage. In summary, we propose that gene expression profiling may have clinical relevance for risk evaluation in MDS at the time of initial diagnosis. Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis.
PMID	12411319
GEOID	
AUTHORS	Hofmann WK,de Vos S,Komor M,Hoelzer D,Wachsman W,Koeffler HP
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 4: Down-regulation
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AB020522,AB022017,AF058989,AF085808,D88797,J03171,L36033,M25897,M55422,M81750,M96956,S69115,S77763,U14575,U18671,U20158,U52521,U78556,X83368,X91809,Y09216,Y16961,Z35227
GENE_SYMBOLS	DLEC1,PRKAA1,PAGE1,UPK3A,PCDHB17P,IFNAR1,CXCL12,PF4,ZNF117,MNDA,CRIPTO3,NKG7,NFE2,PPP1R8,STAT2,LCP2,ARFIP1,MTMR11,PIK3CG,RGS19,DYRK2,TP63,RHOH
FOUNDER_NAMES