ALTERED RETINOIC ACID RECEPTORS

Structurally and functionally altered retinoic acid receptors have bee n associated with rare human neoplasms: acute promyelocytic leukemia a nd hepatocellular carcinoma, Whereas the retinoic acid receptor beta ( RAR beta) rearrangement in hepatocellular carcinoma is unique, in acut e promyelocytic leukemia (APL), RAR alpha fusion to the promyelocytic leukemia (PML) gene by the t(15;11) translocation is a general feature of the disease, APL is an important model in cancer biology because r etinoic 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 molecula r basis of PML/RAR alpha fusion leukemogenesis is discussed with respe ct to dominant negative inhibition of nuclear receptor and PML functio ns.