MLL白血病（MLL-r) 是小儿白血病中的高危病种，存活率低, 寻找早期诊断与新的治疗方法对提高其存活率具有重要的意义。我们前期开展了小儿MLL-r白血病的lncRNA表达谱研究，发现一个在小儿MLL-r患者中表达上调最多的一个lncRNA--LAMP5-AS1。重要的是其表达量与MLL融合蛋白表达量相关，提示LAMP5-AS1很可能是一个核心分子参与到MLL-r 白血病发生的通路中。本项目拟在此基础上开展以下研究：（1）解析LAMP5-AS1在MLL-r 小儿白血病患者中的表达差异及对MLL-r 白血病的发病的影响；（2）阐明LAMP5-AS1如何通过调控自噬相关基因LAMP5影响了MLL融合蛋白的降解；（3）揭示DOT1L结合LAMP5-AS1所介导的表观遗传机制。该项目的完成可为小儿MLL-r白血病的发病机制及针对MLL融合基因的治疗提供新的潜在靶点，具有重要的理论和应用意义 。

The presence of MLL rearrangements，characterized by an exceptionally high incidence of chromosomal translocations affecting the MLL gene is the most important independent predictor of adverse outcome in pediatric leukemia, and the disease often presented as poor prognosis and high mortality. Thus, the distinct mechanisms of disease must be explored to develop a rational basis for the design of novel therapies for the treatment of this disease. LncRNAs have been recently demonstrated as key regulators in cancer progression. We previously carried out a genome-wide lncRNA expression study in MLL-r leukemia patients. A distinct set of lncRNAs associated with the pathways involved in the biological processes of MLL-r leukemia progression were identified. Specifically, we identified a lncRNA, named as LAMP5-AS1 was more highly expressed in pediatric MLL-r leukemia patients and all MLL-r cell lines, suggesting that the lncRNA was apparently associated with the MLL- fusion protein. Based on previous findings, in this study, following studies are initiated: (1) To investigate the role of LAMP5-AS1 in MLL-r leukemia progression and fusion proteindegradation; (2) To figure out the mechanism how LAMP5-AS1 affects the degradation of MLL fusion protein through regulating LAMP5, an autophage associated protein; (3) To investigate the interactions between the lncRNA and DOT1L, a histone H3 methyltransferase, and the the epigenetic mechanisms of LAMP5-AS1/DOT1L mediated in MLL-r leukemogenesis. The study would provide new theoretical basis and therapeutic target for diagnosis and treatment of pediatric MLL-r leukemia.