Hao Rui, Su Lide, Shao Yiming, Bu Na, Ma Liya, Naranmandura Hua
Department of Pharmacology, Inner Mongolia Medical University, Hohhot 010000, China.
School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 May 25;47(5):541-551. doi: 10.3785/j.issn.1008-9292.2018.10.15.
Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (AsO) therapy. APL is a M3 subtype of acute myeloid leukemia (AML), which is characterized by expression of PML-RARα (P/R) fusion protein, leading to the oncogenesis. AsO is currently used as the first-line drug for patients with APL, and the mechanism may be:AsO directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Gene mutations may lead to relapse and drug resistance after AsO treatment. In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with AsO; and explain how PML protein mutations could cause resistance to AsO therapy.
早幼粒细胞白血病（PML）蛋白作为一种肿瘤抑制因子，在接受三氧化二砷（AsO）治疗的急性早幼粒细胞白血病（APL）患者中发挥着重要作用。APL是急性髓系白血病（AML）的M3亚型，其特征在于PML-RARα（P/R）融合蛋白的表达，从而导致肿瘤发生。AsO目前被用作APL患者的一线药物，其作用机制可能是：AsO直接与P/R蛋白的PML部分结合并诱导相关蛋白的多聚化，进而招募不同的功能蛋白以重新形成PML核体（PML-NBs），最终通过SUMO化和泛素化蛋白酶体途径将其降解。基因突变可能导致AsO治疗后复发和耐药。在本综述中，我们讨论了PML蛋白的结构和功能；P/R融合蛋白诱导APL的发病机制；PML蛋白在AsO治疗APL患者中的作用；并解释了PML蛋白突变如何导致对AsO治疗产生耐药性。
