Reconstructing a disease: What essential features of the retinoic acid receptor fusion oncoproteins generate acute promyelocytic leukemia?

Cancer Cell. 2006 Feb;9(2):73-4. doi: 10.1016/j.ccr.2006.01.024.


Acute promyelocytic leukemia (APL) is associated with rearrangement of the retinoic acid receptor alpha (RARalpha) gene leading to the formation of chimeric receptor proteins. In this issue of Cancer Cell, studies by Kwok et al. and Sternsdorf et al. indicate that the ability of the RARalpha oncoproteins to dimerize/multimerize is an essential feature required for the development of disease. Homodimerization allows RARalpha to bind to corepressors with increased affinity and the ability to bind to novel DNA sequences. However, artificial RARalpha dimers were weak oncogenes in vivo, indicating that the fusion partners confer additional properties to RARalpha to efficiently generate disease.

Publication types

  • Comment

MeSH terms

  • Humans
  • Leukemia, Promyelocytic, Acute / metabolism*
  • Leukemia, Promyelocytic, Acute / pathology*
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Binding
  • Receptors, Retinoic Acid / metabolism*
  • Retinoic Acid Receptor alpha
  • Transcription, Genetic / genetics


  • Oncogene Proteins, Fusion
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha