小儿MLL急性淋巴细胞白血病（pediatric MLL-rearranged acute lymphoblastic leukemia，MLL(+) ALL)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治愈率具有重要的意义。我们前期研究发现，miR-27a和miR-29b在MLL(+) ALL病人骨髓细胞中显著低表达，并与MLL融合蛋白特异性招募的甲基化酶DOT1L存在靶向关系，暗示这2个miRNA异常表达及介导的表观遗传机制在小儿MLL白血病中起调控作用。本研究拟在此基础上开展以下研究：(1)验证miRNA在MLL(+) ALL病人中的表达差异及与DOT1L的关系；(2)研究miRNAs在MLL(+) ALL中调控DOT1L所介导的表观遗传机制及对MLL(+) ALL发病的影响。该项目的完成，可为小儿MLL(+) ALL的发病机制提供新的理论依据及潜在治疗靶点

Pediatric MLL-rearranged acute lymphoblastic leukemia (MLL(+) ALL) is one of the highest risk of subsets of pediatric cancer. Patients with pediatric MLL(+) ALL often suffer poor chemotherapy response and high risk of relapse, which induce low event free survival rate. Therefore, it is of crucial significance for improving survival rate to develop early diagnosis and new treatment methods. Our previous studies found that the expressions of two miRNAs, miR-27a and miR-29b, are significantly lower in bone marrow of MLL(+) ALL patients than MLL(-) ALL patients. More importantly, they both directly target to the histone methyltransferase Dot1L, which is recruited by MLL-fusion protein, implying that dysregulated miRNAs might play important roles in pathogenesis of pediatric MLL-rearranged leukemia. Based on previous findings, in this project, following studies are initiated: (1) To figure out if miR-27a and miR-29b involved in MLL(+) ALL pathogenesis and the regulatory relationships between miRNAs and DOT1L; (2) To investigatet the epigenetic mechanisms of miR-27a/miR-29b/DOT1L mediated in leukemogenesis in MLL(+) ALL in vitro and in vivo and elucidate the pathogenesis of miRNAs in the disease. The study would provide new theoretical basis and therapeutic target for diagnosis and treatment of pediatric MLL(+) ALL.