Reconstructing a disease: What essential features of the retinoic acid receptor fusion oncoproteins generate 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.
Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA. jonathan.licht@mssm.edu
Jonathan D
JD
Licht
D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic / Q000235:genetics
D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha