儿童ALL复发与耐药是提高患儿长期无病生存率的主要障碍。我们的前期研究发现CASP8AP2与miR-210低表达均与复发密切相关。已知CASP8AP2与ARS2的相互作用是细胞周期S期进展所必需；ARS2参与miRNA的生成，其沉默导致miR-210水平明显下降。我们推测CASP8AP2与ARS2相互作用参与miR-210生成，CASP8AP2低表达导致miR-210生成减少，造成白血病复发及耐药。拟通过高表达CASP8AP2突变体（缺失与ARS2相互作用的功能域）或沉默ARS2表达，证明CASP8AP2与ARS2相互作用参与miR-210生成；上述细胞经化疗药物处理后凋亡减少，证明miR-210水平与复发、耐药相关。创新点是证明CASP8AP2参与miRNA的生成，从而在ALL复发与耐药中发挥重要作用，有助于阐明儿童ALL中CASP8AP2低表达导致复发与耐药的机制，并提供新的治疗靶点。

Relapse and drug resistance are the main obstacles to the improvement of long-term disease-free survival in childhood ALL. Our previous studies found that patients in low expression groups of CASP8AP2 or miR-210 were subject to relapse. Several studies demonstrated that interaction of CASP8AP2 with ARS2 was necessary for S phase progression; meanwhile, ARS2 was involved in miRNAs biogenesis, and depletion of ARS2 reduced the level of miR-210. We propose that interaction of CASP8AP2 with ARS2 is involved in biogenesis of miR-210, and low expression of CASP8AP2 results in decrease of miR-210 level, which leads to relapse and drug resistance in ALL. This study will verify the role of interaction of CASP8AP2 with ARS2 in biogenesis of miR-210 in ALL cells by overexpression of CASP8AP2 mutant,in which the interacting domain with ARS2 is deleted, or by silencing of ARS2. Furthermore, it will be proved that low level of miR-210 is related with relapse and drug resistance as apoptosis is reduced in above ALL cells after treatment with chemotherapy drugs. This study innovatively demonstrates that CASP8AP2 is involved in miRNA biogenesis, which plays an important role in relapse and drug resistance of ALL. It will help to clarify the mechanism of relapse and drug resistance associated with low expression of CASP8AP2 and to provide new therapeutic targets in childhood ALL.