[The cure for acute promyelocytic leukemia and China's contributions]

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.