A redundant oncogenic potential of the retinoic receptor (RAR) α, β and γ isoforms in acute promyelocytic leukemia

Alterations of the retinoic acid receptor (RAR) a locus are found in 100% of acute promyelocytic leukemia patients, where chromosomal translocations generate the promyelocytic leukemia (PML)-RAR alpha chimeric protein. Here, we have investigated the biological properties of the other RAR isoforms (RAR beta and RAR gamma), through the generation and characterization of artificial PML-RAR'x' fusion proteins. Surprisingly, we found that all of the RAR isoforms share an identical oncogenic potential in vitro, thus implying that the selection of the RAR alpha locus in leukemia patients must occur - rather than through functional differences among the various RAR isoforms - as the consequence of the nuclear architecture of the different RAR loci.