A NOVEL MACROMOLECULAR STRUCTURE IS A TARGET OF THE PROMYELOCYTE-RETINOIC ACID RECEPTOR ONCOPROTEIN

Acute promyelocytic leukemia (APL) is associated with a t(15;17) trans location that creates the promyelocyte-retinoic acid receptor alpha (P ML-RARalpha) fusion gene. Immunohistochemistry demonstrates that PML i s a part of a novel macromolecular organelle (including at least three other nuclear proteins) referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted into a microparticulate pattern as a consequence of the expression of the PML-RAR oncoprotein. RA treatme nt of APL cells triggers a reorganization of PML to generate normal-ap pearing PODs. We propose that PML-RAR is a dominant negative oncoprote in that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel s tructure, but it can be ascribed an imputed function such that its dis ruption leads to altered myeloid maturation; this may represent a nove l oncogenic target.