Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 944, Equipe labellisée par la Ligue Nationale contre le Cancer, 2 University Paris-Diderot, Sorbonne Paris Cité, Paris, France.
J Cell Biol. 2012 Jul 9;198(1):11-21. doi: 10.1083/jcb.201112044.
Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.
急性早幼粒细胞白血病 (APL) 是由染色体易位驱动的，其产物 PML/维甲酸 (RA) 受体 α (RARA) 融合蛋白，影响核受体信号和 PML 体的组装。对 APL 发病机制的剖析导致了 PML 体的重新发现，并揭示了它们在细胞衰老、疾病发病机制和对治疗的反应中的作用。APL 之所以引人注目，是因为偶然发现了两种临床有效的治疗方法，即 RA 和砷，这两种方法都能降解 PML/RARA 癌蛋白，共同治愈 APL。对砷诱导的 PML 或 PML/RARA 降解的分析表明，氧化应激参与了核体的生物发生，SUMO 参与了它们的降解。
