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The FASEB Journal, Vol 10, 955-960, Copyright © 1996 by The Federation of American Societies for Experimental Biology
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H de The
CNRS UPR 9051, Paris, France.
Structurally and functionally altered retinoic acid receptors have been associated with rare human neoplasms: acute promyelocytic leukemia and hepatocellular carcinoma. Whereas the retinoic acid receptor beta (RARbeta) rearrangement in hepatocellular carcinoma is unique, in acute promyelocytic leukemia (APL), RARalpha fusion to the promyelocytic leukemia (PML) gene by the t(15;17) translocation is a general feature of the disease. APL is an important model in cancer biology because retinoic acid induces complete remissions in this malignancy, providing the first example of differentiation therapy and of an antineoplastic drug directly targeted at the underlying genetic lesion. The molecular basis of PML/RARalpha fusion leukemogenesis is discussed with respect to dominant negative inhibition of nuclear receptor and PML functions.
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