PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia.
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.