STANDARD_NAME	NEBEN_AML_WITH_FLT3_OR_NRAS_DN
SYSTEMATIC_NAME	M12530
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NEBEN_AML_WITH_FLT3_OR_NRAS_DN
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes down-regulated in acute myeloid leukemia (AML) samples with constitutively activated FLT3 [GeneID=2322] or with activating point mutations within NRAS [GeneID=4893].
DESCRIPTION_FULL	In acute myeloid leukemia (AML), constitutive activation of the FLT3 receptor tyrosine kinase, either by internal tandem duplications (FLT3-ITD) of the juxtamembrane region or by point mutations in the second tyrosine kinase domain (FLT3-TKD), as well as point mutations of the NRAS gene (NRAS-PM) are among the most frequent somatic gene mutations. To elucidate whether these mutations cause aberrant signal transduction in AML, we used gene expression profiling in a series of 110 newly diagnosed AML patients with normal karyotype. The different algorithms used for data analysis revealed highly concordant sets of genes, indicating that the identified gene signatures are specific for each analysed subgroup. Whereas samples with FLT3-ITD and FLT3-TKD could be separated with up to 100% accuracy, this did not apply for NRAS-PM and wild-type samples, suggesting that only FLT3-ITD and FLT3-TKD are associated with an apparent signature in AML. The set of discriminating genes included several known genes, which are involved in cell cycle control (CDC14A, WEE1), gene transcription (HOXB5, FOXA1), and signal transduction (SMG1). In conclusion, we showed that unique gene expression patterns can be correlated with FLT3-ITD and FLT3-TKD. This might lead to the identification of further pathogenetic relevant candidate genes particularly in AML with normal karyotype.
PMID	15674343
GEOID	
AUTHORS	Neben K,Schnittger S,Brors B,Tews B,Kokocinski F,Haferlach T,Müller J,Hahn M,Hiddemann W,Eils R,Lichter P,Schoch C
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 2: Fold change < -2
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	CCT8,CDC14A,CYP2J2,HSPA5,KIF23,LDHB,PKMYT1,RAC2,RPL28,RPS3,SERPINH1,WEE1
GENE_SYMBOLS	CCT8,CDC14A,CYP2J2,HSPA5,KIF23,LDHB,PKMYT1,RAC2,RPL28,RPS3,SERPINH1,WEE1
FOUNDER_NAMES