Asou Norio
Department of Hematology, International Medical Center, Saitama Medical University.
Rinsho Ketsueki. 2018;59(6):725-734. doi: 10.11406/rinketsu.59.725.
Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML) -retinoic acid receptor (RAR) α fusion protein generated by the chromosomal translocation t (15;17) which affects both nuclear receptor signaling and PML nuclear body (NB) assembly. The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARα has been a major breakthrough in APL treatment. ATRA and ATO target RARα and PML, respectively, and elicit PML-RARα degradation, leading to the reformation of normal NBs and cell differentiation. In several multicenter trials, more than 90% of newly diagnosed APL patients treated with ATRA and chemotherapy achieved complete remission, of whom 20%-30% subsequently relapsed; the overall survival was approximately 80% in these studies. However, several major clinical problems continue to account for treatment failure including early death due to hemorrhage, infection during consolidation, disease relapse, and secondary malignancies. These issues are associated mainly with anticancer agents used in combination with ATRA. Combination therapy using ATRA and ATO is the current standard therapy for untreated patients with APL in Western countries. The current problems in patients with APL treated with ATRA and ATO are APL differentiation syndrome and high risk of relapse in patients with an initial leukocyte count of more than 10×10/l.
急性早幼粒细胞白血病（APL）由染色体易位t（15；17）产生的早幼粒细胞白血病（PML）-维甲酸受体（RAR）α融合蛋白驱动，该易位影响核受体信号传导和PML核体（NB）组装。全反式维甲酸（ATRA）和三氧化二砷（ATO）作为针对PML-RARα的分子靶向疗法的出现是APL治疗的一项重大突破。ATRA和ATO分别靶向RARα和PML，并引发PML-RARα降解，导致正常核体重组和细胞分化。在多项多中心试验中，超过90%接受ATRA和化疗的新诊断APL患者实现了完全缓解，其中20%-30%随后复发；这些研究中的总生存率约为80%。然而，几个主要的临床问题仍然导致治疗失败，包括出血导致的早期死亡、巩固期感染、疾病复发和继发性恶性肿瘤。这些问题主要与与ATRA联合使用的抗癌药物有关。在西方国家，使用ATRA和ATO的联合疗法是未治疗的APL患者的当前标准疗法。接受ATRA和ATO治疗的APL患者当前存在的问题是APL分化综合征以及初始白细胞计数超过10×10⁹/L的患者复发风险高。
