Systematic name M1430
Brief description Genes defining differentiation potential of the bipotential myeloid cell line FDB.
Full description or abstract Mechanisms controlling the balance between proliferation and self-renewal versus growth suppression and differentiation during normal and leukemic myelopoiesis are not understood. We have used the bi-potent FDB1 myeloid cell line model, which is responsive to myelopoietic cytokines and activated mutants of the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, having differential signaling and leukemogenic activity. This model is suited to large-scale gene-profiling, and we have used a factorial time-course design to generate a substantial and powerful data set. Linear modeling was used to identify gene-expression changes associated with continued proliferation, differentiation, or leukemic receptor signaling. We focused on the changing transcription factor profile, defined a set of novel genes with potential to regulate myeloid growth and differentiation, and demonstrated that the FDB1 cell line model is responsive to forced expression of oncogenes identified in this study. We also identified gene-expression changes associated specifically with the leukemic GM-CSF receptor mutant, V449E. Signaling from this receptor mutant down-regulates CCAAT/enhancer-binding protein alpha (C/EBPalpha) target genes and generates changes characteristic of a specific acute myeloid leukemia signature, defined previously by gene-expression profiling and associated with C/EBPalpha mutations.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16769770   Authors: Brown AL,Wilkinson CR,Waterman SR,Kok CH,Salerno DG,Diakiw SM,Reynolds B,Scott HS,Tsykin A,Glonek GF,Goodall GJ,Solomon PJ,Gonda TJ,D'Andrea RJ
Exact source Table 3S
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Organism Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
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Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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