STANDARD_NAME GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP SYSTEMATIC_NAME M14833 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP NAMESPACE MOUSE_GENE_SYMBOL DESCRIPTION_BRIEF Up-regulated genes from the set B (Fig. 5a): specific signature shared by cells expressing either AF4-MLL or MLL-AF4 [GeneID=4299;4297] 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 BS FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 2700008B19Rik,4833416E15Rik,4933407K13Rik,Adam12,AI426953,BC013481,Cd79b,Cib2,Clec2d,Col11a1,Crlf1,D10Ertd438e,Dnajc12,Gabra6,Galnt12,Gpr73,Ifi1,Nrxn1,Omd,Parp12,Ppp1r3c,Prkwnk3,Ranbp2,Runx3,Tcn2,Usp9x,Xist,Zfp533 GENE_SYMBOLS HEATR6,ENPP1,,BTG1,ADAM12,RBM47,CD79B,CIB2,CLEC2D,COL11A1,CRLF1,NUS1,DNAJC12,GABRA6,GALNT12,PROKR1,IRGM,NRXN1,OMD,PARP12,PPP1R3C,WNK3,RANBP2,RUNX3,TCN2,USP9X,XIST,ZNF385B FOUNDER_NAMES