急性髓系白血病（AML）伴有t(8;21)染色体异常是一特殊亚型。此类患者以低中危组为主，但治疗转归差别大，30%患者预后极差，提示目前分层体系仍存在不足，诊疗异质性机制尚不明。前期研究发现，即使同一染色体易位累及的AML在初诊时白血病细胞就存在多个亚克隆，且在治疗过程中白血病细胞发生不同的克隆演化，这些都直接影响了临床治疗转归。本研究将在前期研究基础上，整合基因组、转录组、表观组测序及高通量热点突变基因靶向深度测序技术，对t(8;21)AML初发、治疗不同阶段、复发等多个时间点的白血病亚克隆进行动态跟踪，解析该亚型白血病克隆异质性及演化的规律，从而揭示临床缓解、耐药和复发的分子机制；并通过细胞及动物实验，挖掘候选基因并验证其功能。通过本研究将建立t(8;21)AML基于克隆演化的精准分子分型及预后体系，以指导临床个体化精准治疗。

Acute myeloid leukemia (AML) with t (8;21) is generally considered as a unique sub-type with similar genetic background. Patients in this cytogenetic group are considered with low or intermediate risk and often treated similarly. However, the treatment outcome varies dramatically among the patients, in which 30% of them show very poor prognosis, suggesting that the current cytogenetic/molecular risk stratification is far from complete and the underlying mechanism of disease heterogeneity is unclear yet. In our pilot study, we found that (i) patients with the same chromosome abnormality harbored the distinct sub-clones during disease onset and (ii) patients with AML in morphological remission continued to have clonal hematopoiesis with populations based on the founding AML clone during treatment. These preliminary data suggested that clonal evolution of AML may have direct impact on treatment outcome and confer an increased risk of relapse. In this study, we will combine genome, transcriptome, epigenetic and hot spot targeted deep sequencing technology to analyze the dynamic change of leukemic sub-clones at disease onset, during the treatment process and at relapse in t (8;21) AML. This comprehensive analysis may reveal the clonal heterogeneity and evolution pattern of t (8;21) AML and help to understand the molecular mechanisms of treatment remission, resistance and relapse. In the future, we hope that our study will build the foundation of clonal evolution based precise genomic classification in t (8;21) AML and guide the individualized leukemia treatment.