Chen L, Chen S J
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Department of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhonghua Xue Ye Xue Za Zhi. 2025 May 14;46(5):377-384. doi: 10.3760/cma.j.cn121090-20250307-00119.
Acute promyelocytic leukemia (APL) was historically regarded as the most aggressive subtype of acute leukemia due to its high early mortality rate. The transformation in APL treatment represents a milestone in targeted cancer therapy. The discovery and clinical application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have dramatically improved the prognosis of APL, increasing the 5-year overall survival rate from less than 35% to over 90%. Chinese hematology/oncology community have made significant contributions to this transformation: Professor Wang Zhenyi's group pioneered ATRA-induced differentiation therapy, while Professor Zhang Tingdong's group verified the clinical efficacy of ATO. The research team of Shanghai Institute of Hematology (SIH) cloned the PML::RARA fusion gene resulting from the chromosomal translocation (15;17) and the first variant PLZF::RARA fusion gene. Based on the characterization of the leukogenesis at molecular and cellular levels and the mechanisms of action of effective drugs, the SIH team established a synergistic targeted therapy protocol for newly diagnosed APL patients, achieving a disease-free survival rate of 95.7% in a nationwide multi-center clinical trial. Subsequently, several teams explored the use of oral arsenic (Realgar-Indigo naturalis formula or oral ATO solution) combined with ATRA to treat APL, which is of high cost-effectiveness and can be promoted in resource-restricted regions. This review systematically summarizes the key therapeutic breakthroughs in APL, elucidates the underlying scientific mechanisms and clinical significance, and identifies remaining challenges for optimizing disease management.
急性早幼粒细胞白血病(APL)在历史上因其早期死亡率高而被视为急性白血病中最具侵袭性的亚型。APL治疗的变革是靶向癌症治疗的一个里程碑。全反式维甲酸(ATRA)和三氧化二砷(ATO)的发现及临床应用显著改善了APL的预后,使5年总生存率从不到35%提高到了90%以上。中国血液学/肿瘤学界对这一变革做出了重大贡献:王振义教授团队开创了ATRA诱导分化疗法,张亭栋教授团队验证了ATO的临床疗效。上海血液学研究所(SIH)的研究团队克隆了由染色体易位(15;17)产生的PML::RARA融合基因以及首个变异体PLZF::RARA融合基因。基于在分子和细胞水平对白血病发生机制及有效药物作用机制的研究,SIH团队为新诊断的APL患者建立了协同靶向治疗方案,在全国多中心临床试验中实现了95.7%的无病生存率。随后,多个团队探索了使用口服砷剂(雄黄-靛蓝天然配方或口服ATO溶液)联合ATRA治疗APL,该方法具有高成本效益,可在资源有限地区推广。本综述系统总结了APL治疗的关键突破,阐明了其潜在的科学机制和临床意义,并确定了优化疾病管理方面尚存的挑战。