Gene Set: GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP

Standard name GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP
Systematic name M18095
Brief description Up-regulated genes from the set G (Fig. 5a): specific to cells expressing both MLL-AF4 [GeneID=4297;4299] and AF4-MLL fusion proteins.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17130830   Authors: Gaussmann A,Wenger T,Eberle I,Bursen A,Bracharz S,Herr I,Dingermann T,Marschalek R
Exact source Table GS
Related gene sets (show 13 additional gene sets from the source publication)

(show 2 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform MOUSE_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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