Effects of realgar (As4S4) on degradation of PML-RARA harboring acquired arsenic-resistance mutations.
Effects of realgar (As4S4) on degradation of PML-RARA harboring acquired arsenic-resistance mutations.
复制标题
雄黄 (As4S4) 对含有获得性砷抗性突变的 PML-RARA 降解的影响。
DOI：
10.1007/s00277-017-3093-8
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Xu Kailin
中科院分区：
文献类型：
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作者：
Niu Mingshan;Shen Yangling;Qi Jialei;Liu Xuejiao;Sang Wei;Wu Qingyun;Cao Jiang;Chen Wei;Yao Yao;Xu Kailin
急性早幼粒细胞白血病（APL）的特征是血液和骨髓中异常早幼粒细胞的积累和特异性染色体易位t（15; 17）（q24）。1; q21. 1）。t（15; 17）将17号染色体上的视黄酸受体-α基因（RARA）与15号染色体上的早幼粒细胞白血病基因（PML）融合，产生PML-RARA融合蛋白，该融合蛋白是APL的关键驱动因子和治疗靶标[1]。三氧化二砷已被证明是APL中最活跃的单一药物[2]。三氧化二砷通过直接结合PML部分并触发PML-RARA癌蛋白的降解来治疗APL。然而，在砷耐药APL患者中发现了一组PML点突变，这些患者的结局极差[3，4]。应评估突变是否导致临床耐药。
Dear Editor, Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in blood and bone marrow and the specific chromosomal translocation t (15; 17)(q24. 1; q21. 1). The t (15; 17) fuses the retinoic acid receptor-alpha gene (RARA) on chromosome 17 with the promyelocytic leukemia gene (PML) on chromosome 15, resulting in PML-RARA fusion protein that is the key driver and therapy target of APL [1]. Arsenic trioxide has been shown to be the most active single agent in APL [2]. Arsenic trioxide cures APL by directly binding to the PML moiety and triggering the degradation of PML-RARA oncoprotein. However, it has been identified a panel of PML point mutations in arsenic-resistant APL patients, and the outcomes of these patients are extremely poor [3, 4]. Evaluation of whether the mutations contributes to clinical resistance should be performed.