Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure. PML nuclear bodies are druggable and could be harnessed in other conditions.

中文翻译：

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急性早幼粒细胞白血病：癌蛋白靶向治疗的范例。

最近的临床试验表明，结合两种靶向疗法：视黄酸（RA）和砷，可以彻底治愈绝大多数急性早幼粒细胞白血病（APL）患者。鼠标模型为涉及的机制提供了意想不到的见解。在RA和/或砷引发的PML / RARA降解后恢复PML核体是必不可少的，而RA触发的转录激活对于根除APL则是必不可少的。在耐治疗的患者中已检测到PML / RARA的砷结合位点以及PML的突变，证明了PML在APL治愈中的关键作用。PML核体是可药物化的，可以在其他条件下加以利用。