MLL translocations, histone modifications and leukaemia stem-cell development

Nat Rev Cancer. 2007 Nov;7(11):823-33. doi: 10.1038/nrc2253.

Abstract

Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis. The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4), and positively regulates gene expression including multiple Hox genes. Leukaemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform haematopoietic cells into leukaemia stem cells. The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Cell Division / physiology
  • Cell Transformation, Neoplastic / genetics
  • Child
  • Chromatin / ultrastructure
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation* / genetics
  • Gene Expression Regulation* / physiology
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / physiology*
  • Histones / metabolism*
  • Humans
  • Infant
  • Leukemia / genetics*
  • Methylation
  • Mice
  • Myeloid-Lymphoid Leukemia Protein / chemistry
  • Myeloid-Lymphoid Leukemia Protein / deficiency
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Myeloid-Lymphoid Leukemia Protein / physiology*
  • Neoplastic Stem Cells / cytology
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / physiology
  • Prognosis
  • Protein Methyltransferases
  • Protein Processing, Post-Translational

Substances

  • Chromatin
  • Histones
  • KMT2A protein, human
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Kmt2a protein, mouse