急性早幼粒细胞白血病：一种针对癌蛋白的靶向治疗范例。
Acute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure.
机构信息
Collège de France, PSL Research University, Chaire d'Oncologie Cellulaire et Moléculaire, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR 944, CNRS UMR 7212, Hôpital St. Louis, Paris, France.
Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
出版信息
Cancer Cell. 2017 Nov 13;32(5):552-560. doi: 10.1016/j.ccell.2017.10.002.
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.
最近的临床试验表明，绝大多数急性早幼粒细胞白血病（APL）患者可以通过两种靶向治疗的联合治疗得以根治：维甲酸（RA）和砷剂。小鼠模型为相关机制提供了意想不到的见解。RA 和/或砷剂起始的 PML/RARA 降解导致 PML 核体的恢复是至关重要的，而 RA 触发的转录激活对于 APL 的消除是可有可无的。在治疗耐药的患者中已经检测到 PML/RARA 的砷结合位点突变，以及 PML 突变，这表明 PML 在 APL 治愈中的关键作用。PML 核体是可用药的，并且可以在其他情况下加以利用。
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