MLL: a histone methyltransferase disrupted in leukemia

Trends Mol Med. 2004 Oct;10(10):500-7. doi: 10.1016/j.molmed.2004.08.005.

Abstract

Rearrangements of the MLL gene, which is located at chromosome 11q23, are associated with aggressive acute leukemias in both children and adults. MLL regulates Hox gene expression through direct promoter binding and histone modification. MLL rearrangements occurring in leukemia include MLL fusion genes, partial tandem duplications of MLL and MLL amplification. MLL fusions and amplification upregulate Hox expression, apparently resulting in a block of hematopoietic differentiation. Future therapies for MLL-associated leukemia might involve blocking Hox gene upregulation by using fusion proteins or inhibiting the activity of Hox proteins themselves.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Gene Amplification
  • Gene Duplication
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Leukemia / genetics*
  • Models, Genetic
  • Myeloid-Lymphoid Leukemia Protein
  • Protein Methyltransferases
  • Proto-Oncogenes / genetics*
  • Recombinant Fusion Proteins / genetics
  • Transcription Factors / genetics*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase