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Cell. 1994 Jan 28;76(2):333-43.

A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein.

Author information

1
Biomedical Sciences Graduate Progam University of California, San Diego, La Jolla 92037.

Abstract

Acute promyelocytic leukemia (APL) is associated with a t(15;17) translocation that creates the promyelocyte-retinoic acid receptor alpha (PML-RAR alpha) fusion gene. Immunohistochemistry demonstrates that PML is 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 treatment of APL cells triggers a reorganization of PML to generate normal-appearing PODs. We propose that PML-RAR is a dominant negative oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel structure, but it can be ascribed an imputed function such that its disruption leads to altered myeloid maturation; this may represent a novel oncogenic target.

PMID:
8293467
DOI:
10.1016/0092-8674(94)90340-9
[Indexed for MEDLINE]

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