The SIGnaling Network
Open Resource

Pathway ID: SIGNOR-AML1-ETO

Description: The t(8;21) (q21;q22) translocation is among the commonest rearrangements in AML, causing enhanced marrow granulopoiesis with inhibition of erythropoiesis. This translocation causes the formation of the fusion oncoprotein AML1 (chr.21)-ETO (chr.8) joining the transcription factor RUNX1/AML1 fused to ETO. The N-terminal of AML1 interact with CBFb and with RUNX1 DNA binding sites, while ETO recruits a nuclear corepressor complex resulting in the dominant repression of AML1-regulated target genes involved in granulocytic differentiation (i.e. Myeloperoxidase, CDKN2A/p14ARF). CD45/PTPRC, a protein tyrosine phosphatase that acts as a negative regulator of cytokine/growth factor receptor and JAK/STAT signaling is also repressed. AML1/ETO directly interferes with recruitment of essential cofactors by a number of crucial hematopoietic transcription factors such as C/EBPα and PU.1/SPI1. AML1-ETO can also activate genes involved in stem cell self-renewal: Jagged and HES1 (Notch pathway) or Plakoglobin, which binds TCF/LEF and activates the Wnt target genes C-MYC and CYCLIN D1. PMID: 17125917

Curated by: irozzo