PAX5突变是B急淋重要的发病因素，PAX5突变种类多，限制了针对PAX5突变的靶向治疗。芯片信息分析说明:尽管PAX5突变种类多,但PAX5突变具有类似的基因指纹，PAX5下游靶基因有可能成为多种PAX5突变的治疗靶点。ZNRF1是我们筛选的PAX5突变的下游靶基因，目前对ZNRF1的认识有限，对其在肿瘤发生中的作用没有研究。目前研究认为ZNRF1 作为E3连接酶，可通过调控AKT和微管蛋白参与神经细胞的再生。我们认为：在PAX5突变的B急淋中，ZNRF1表达下降通过调控AKT和微管蛋白，参与急淋发生，通过上调ZNRF1表达对PAX5突变的急淋有靶向作用。本项目通过体内外实验研究上调ZNRF1表达对PAX5突变急淋的作用，并阐明ZNRF1缺失在急淋发生的机制。完成该项目，将加深对ZNRF1的认识，进一步阐明PAX5突变导致急淋的机制，为PAX5突变急淋的靶向治疗提供新策略。

PAX5 is important altered in B-cell acute lymphoblastic leukemia (ALL), takes part in leukemogenesis, and would be the target for therapy in ALL. Complexity of PAX5 alterations blocks the advancement of PAX5 targeted therapy. We found cases of PAX5 alterations had same gene expression signatures, and this hints PAX5 downstream genes would be the target for therapy in PAX5 alterations ALL. Using bioinformatical methods, we characterized one E3 ligase, ZNRF1, which is not known in cancer research. ZNRF1 regulates neuritogenesis via tubulin and AKT. We hypothesize that ZNRF1 may take part in leukemogenesis of ALL with PAX5 alterations. We study the role of ZNRF1 in leukemogenesis of ALL with PAX5 alterations, and this will provide new strategy for ALL.