University Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis 1, Avenue Claude Vellefaux, 75475 Paris, Cedex 10, France.
Trends Mol Med. 2012 Jan;18(1):36-42. doi: 10.1016/j.molmed.2011.10.001. Epub 2011 Nov 4.
Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the PML/RARA oncogene. The prognosis for patients with APL was revolutionized by two treatments: retinoic acid (RA) and As(2)O(3) (arsenic trioxide). These were both shown a posteriori to target PML/RARA, explaining their exquisite specificity for APL. Arsenic, as a single agent, cures up to 70% of patients, whereas APL patients treated with the combination of RA and As(2)O(3) reach a stunning 90% cure rate. Recent physiopathological models highlight the key role of RA- and As(2)O(3)-triggered PML/RARA degradation, and the molecular mechanisms underlying As(2)O(3)-induced PML/RARA degradation have been recently clarified. As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA.
急性早幼粒细胞白血病 (APL) 是一种由 PML/RARA 癌基因驱动的血液系统恶性肿瘤。两种治疗方法改变了 APL 患者的预后：维甲酸 (RA) 和 As2O3（三氧化二砷）。这两种方法都被证明可以靶向 PML/RARA，解释了它们对 APL 的特异性。砷单独使用可治愈多达 70%的患者，而接受 RA 和 As2O3 联合治疗的 APL 患者的治愈率高达 90%。最近的生理病理模型强调了 RA 和 As2O3 触发的 PML/RARA 降解的关键作用，并且最近阐明了砷诱导的 PML/RARA 降解的分子机制。如下所述，砷结合、氧化、PML 核体内的 SUMO 化以及 RNF4 介导的泛素化都有助于 As2O3 触发的 PML/RARA 代谢。
