全反式维甲酸（ATRA）联合三氧化二砷（ATO）使急性早幼粒细胞白血病（APL）从高度致命的白血病转变为可“治愈”的白血病，但依然无法避免高危APL患者的早期死亡（ED）现象，这是目前公认的刻不容缓的临床问题。临床及基础研究表明，现有的预后指标、免疫分型及分子生物学标志并不能全面解释ED错综复杂的原因。前期工作中，我们对ED与非ED患者的全基因组、全转录组以及体内药物反应性进行研究，发现ED患者中有细胞增殖、迁移、粘附、炎性、免疫、分化、纤溶、耐药等多种差异基因表达。本课题将在前期多层面、时间序列的全景式组学研究基础上，识别ED发生相关的基因结构变异及在治疗过程中的变化，解析与高白细胞、出血、药物反应等因素的关系，并扩大样本验证和功能探索，提出基于分子生物学水平的、针对APL-ED的新型危险分层方法，为高ED风险的APL患者提供精准治疗的靶点，为实现彻底治愈APL提出一定的理论和实践基础。

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have made acute promyelocytic leukemia (APL) from highly fatal to highly curable. However, combination therapy did not solve the problem of early death (ED) in high-risk APL patients, which remains the most urgent issue for the treatment of APL. Clinical and basic studies have shown that, the current prognostic factors, immunophenotypes and biomarkers are not able to explain the complicated reasons of ED. In the previous studies, we compared ED patients with non-ED patients by whole-genome sequencing, RNA-seq and in-vivo drug reaction, and found that ED patients had plenty of differential genes expression, involving cell proliferation, migration, adhesion, inflammatory and immune responses, differentiation, fibrinolysis and resistance of drugs. Based on the multi-layer, time-series, panoramic-omics results above, we will continue to find the structural and treatment variation of ED-related genes, and to uncover the relationships between those differential genes with high white blood cell count, hemorrhage and drug reaction. Furthermore, the differential genes will be validated by sample addition and functional verification. Thus we shall promote a new ED risk stratification system to APL patients on the basis of molecular biology, indicating potential target treatment for thoroughly curing the disease.