Determinants of Oncogenic Transformation in Acute Promyelocytic Leukemia: The Hetero-Union Makes the Force

Acute promyelocytic leukemia (APL) is caused by chromosomal translocations that involve the retinoic acid receptor α (RAR) and several other genes to yield X-RAR fusion proteins. Unlike wild-type RARs, which require heterodimerization with the retinoid X receptor (RXR) for their function as DNA-binding transcriptional regulators, X-RAR fusion proteins bind DNA and deregulate transcription as homo-oligomers. In this issue of Cancer Cell, however, Zeisig et al. and Zhu et al. show that RXR recruitment is a critical determinant for the transforming potential of oligomeric X-RAR fusion proteins and explore the possibility for targeted interventions in APL with either RAR or RXR ligands.