Dyck J A, Maul G G, Miller W H, Chen J D, Kakizuka A, Evans R M
Biomedical Sciences Graduate Progam University of California, San Diego, La Jolla 92037.
Cell. 1994 Jan 28;76(2):333-43. doi: 10.1016/0092-8674(94)90340-9.
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.
急性早幼粒细胞白血病（APL）与t(15;17)易位相关，该易位产生早幼粒细胞-维甲酸受体α（PML-RARα）融合基因。免疫组织化学显示，PML是一种新型大分子细胞器（至少包括其他三种核蛋白）的一部分，该细胞器被称为PML致癌结构域（PODs）。在APL细胞中，由于PML-RAR癌蛋白的表达，POD被破坏成微粒状模式。用维甲酸（RA）处理APL细胞会引发PML的重组，从而产生外观正常的POD。我们提出，PML-RAR是一种显性负癌蛋白，它通过抑制POD的组装发挥其假定的致白血病作用。根据这一观点，POD不仅是一种新型结构，而且可以赋予其一种假定功能，即其破坏会导致髓系成熟改变；这可能代表一个新的致癌靶点。
