B细胞急性淋巴细胞白血病（B-cell acute lymphoblastic leukemia，B-ALL）是最常见的儿童恶性肿瘤。基于危险度分层治疗的诊疗方案已经使得儿童B-ALL的5年总体生存率上升至85%以上，但仍有10-15%的患儿发生复发。克隆演变是B-ALL复发的内在动力，化疗耐药是B-ALL复发的本质，但克隆演变的规律和化疗耐药的机制尚不完全清楚。在前期工作中，通过对一名复发B-ALL患儿进行多组学测序，我们初步发现了B-ALL克隆演变的规律及耐药复发的机制。在此基础上，本课题拟对8名复发B-ALL患儿初诊、缓解和复发等不同时间点白血病细胞进行全基因组，转录组和单细胞转录组测序，结合大规模临床标本验证及体内外功能实验，揭示复发B-ALL克隆演化规律及复发机制，筛选靶向小分子化合物，开发精准治疗复发B-ALL的诊疗方案，提升我国儿童B-ALL的诊疗水平。

B-cell acute lymphoblastic leukemia is the most common malignancy affecting children. Outcomes for children improved over the last 50 years due to the advent of multidrug, risk-adapted chemotherapy and the recognition of clinical, biological, and treatment response characteristics that identify patients at risk for treatment failure. Cure rate are now approximately 85%. However, the prognosis for the 10-15% of children who relapse remains dismal and has not improved over the past two decades. Clonal evolution and drug resistance drive the initiation of relapse of pediatric B-ALL. However, the mechanism of clonal evolution and resistance upon chemotherapy drugs are still unclear. In our previous study, we had investigated the clonal evolution and drug resistance via whole genome sequence, RNA sequence and single cell transcription sequence and we found that mutation of PDGFRB C843 played a critical role in the drug resistance. Based on this study, we plan to investigate the clonal evolution and drug resistance of relapse B-ALL via whole genome sequence, RNA sequence and single cell transcription sequence of 8 relapsed B-All samples. Out study will clarify the clonal evolution and the mechanism of B-ALL relapse and shed light on the precise therapy of relapse pediatric B-ALL patients.