STANDARD_NAME	GAUSSMANN_MLL_AF4_FUSION_TARGETS_D_DN
SYSTEMATIC_NAME	M527
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GAUSSMANN_MLL_AF4_FUSION_TARGETS_D_DN
NAMESPACE	MOUSE_GENE_SYMBOL
DESCRIPTION_BRIEF	Down-regulated genes from the set D (Fig. 5a): specific signature shared by cells expressing MLL-AF4 [GeneID=4297;4299] alone and those expressing both MLL-AF4 and AF4-MLL fusion proteins.
DESCRIPTION_FULL	The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapy-related high-risk acute leukemia. Here, we investigated the biological effects of MLL.AF4, AF4.MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several parameters like cell growth, cell cycling capacity, apoptotic behavior and growth transformation were investigated under physiological and stress conditions. Co-transfected cells displayed the highest resistance against apoptotic triggers, cell cycling capacity and loss-of-contact inhibition. These analyses were complemented by gene expression profiling experiments and specific gene signatures were established for each of the three cell lines. Interestingly, co-transfected cells strongly upregulate the homeobox gene Nanog. In combination with Oct4, the Nanog homeoprotein is steering maintenance of pluripotency and self-renewal in embryonic stem cells. Transcription of Nanog and other stem cell factors, like Oct4 and Bmi1, was verified in biopsy material of t(4;11) patient cells which express both reciprocal t(4;11) fusion genes. In conclusion, the presence of both reciprocal MLL fusion proteins confers biological properties known from t(4;11) leukemia, suggesting that each of the two fusion proteins contribute specific properties and, in combination, also synergistic effects to the leukemic phenotype.
PMID	17130830
GEOID	
AUTHORS	Gaussmann A,Wenger T,Eberle I,Bursen A,Bracharz S,Herr I,Dingermann T,Marschalek R
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table DS
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	2610305D13Rik,5730405I09Rik,Acpl2,Afp,Aldh1a1,Dusp4,Gpc1,Gpc6,MGI:2176230,Slc35c2
GENE_SYMBOLS	,CCNY,PXYLP1,AFP,ALDH1A1,DUSP4,GPC1,GPC6,APOBR,SLC35C2
FOUNDER_NAMES