A tumorigenic MLL-homeobox network in human glioblastoma stem cells

Cancer Res. 2013 Jan 1;73(1):417-27. doi: 10.1158/0008-5472.CAN-12-1881. Epub 2012 Oct 29.


Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity of the epigenetic modifiers Polycomb and Trithorax complexes may contribute to the neoplastic phenotype. Here, we provide the first mechanistic insights into the role of the Trithorax protein mixed lineage leukemia (MLL) in maintaining cancer stem cell characteristics in human glioblastoma. We found that MLL directly activates the Homeobox gene HOXA10. In turn, HOXA10 activates a downstream Homeobox network and other genes previously characterized for their role in tumorigenesis. The MLL-Homeobox axis we identified significantly contributes to the tumorigenic potential of glioblastoma stem cells. Our studies suggest a role for MLL in contributing to the epigenetic heterogeneity between tumor-initiating and non-tumor-initiating cells in glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Genes, Homeobox / physiology*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Myeloid-Lymphoid Leukemia Protein / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction


  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase