Alterations of the retinoic acid receptor (RAR)α locus are found in 100% of acute promyelocytic leukemia patients, where chromosomal translocations generate the promyelocytic leukemia (PML)-RARα chimeric protein. Here, we have investigated the biological properties of the other RAR isoforms (RARβ and RARγ), 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 RARα 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.
A redundant oncogenic potential of the retinoic receptor (RAR) alpha, beta and gamma isoforms in acute promyelocytic leukemia / A. Marinelli, D. Bossi, P.G. Pelicci, S. Minucci. - In: LEUKEMIA. - ISSN 0887-6924. - 21:4(2007 Apr), pp. 647-650.
A redundant oncogenic potential of the retinoic receptor (RAR) alpha, beta and gamma isoforms in acute promyelocytic leukemia
P.G. PelicciPenultimo
;S. Minucci
2007
Abstract
Alterations of the retinoic acid receptor (RAR)α locus are found in 100% of acute promyelocytic leukemia patients, where chromosomal translocations generate the promyelocytic leukemia (PML)-RARα chimeric protein. Here, we have investigated the biological properties of the other RAR isoforms (RARβ and RARγ), 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 RARα 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.Pubblicazioni consigliate
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