Cell of Origin in AML: Susceptibility to MN1-Induced Transformation Is Regulated by the MEIS1/AbdB-like HOX Protein Complex Journal Articles uri icon

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  • Pathways defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.


  • Heuser, Michael
  • Yun, Haiyang
  • Berg, Tobias
  • Yung, Eric
  • Argiropoulos, Bob
  • Kuchenbauer, Florian
  • Park, Gyeongsin
  • Hamwi, Iyas
  • Palmqvist, Lars
  • Lai, Courteney K
  • Leung, Malina
  • Lin, Grace
  • Chaturvedi, Anuhar
  • Thakur, Basant Kumar
  • Iwasaki, Masayuki
  • Bilenky, Mikhail
  • Thiessen, Nina
  • Robertson, Gordon
  • Hirst, Martin
  • Kent, David
  • Wilson, Nicola K
  • Göttgens, Bertie
  • Eaves, Connie
  • Cleary, Michael L
  • Marra, Marco
  • Ganser, Arnold
  • Humphries, R Keith

publication date

  • July 2011

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