Altered ligand binding and transcriptional regulation by mutations in the PML/RARα ligand-binding domain arising in retinoic acid–resistant patients with acute promyelocytic leukemia

Abstract excerpt

Acute promyelocytic leukemia (APL) is characterized by a specific translocation, t(15;17), that fuses the promyelocytic leukemia (PML) gene with the RA receptor RARalpha. Pharmacologic doses of retinoic acid (RA) induce differentiation in human APL cells and complete clinical remissions. Unfortunately, APL cells develop resistance to RA in vitro and in vivo. Recently, mutations in PML/RARalpha have been described...

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