急性髓细胞白血病（AML）是儿童死亡率很高的恶性肿瘤，启动子异常甲基化导致肿瘤抑制基因失活是推动AML发生、发展的关键因素之一。双特异性蛋白磷酸酶16(DUSP16)是我们使用大样本筛选发现儿童AML中异常甲基化的重要基因。进一步研究发现DUSP16的异常甲基化与儿童AML病人预后密切相关；过表达DUSP16明显促进AML细胞的凋亡和细胞G1期阻滞；DUSP16具有对组蛋白H3去磷酸化修饰的新作用。以此为切入点，本项目拟进一步明确DUSP16是否为AML相关肿瘤抑制基因，系统研究DUSP16对组蛋白H3的去磷酸化作用，揭示DUSP16异常甲基化导致组蛋白H3磷酸化失控的致病作用和分子机制。在儿童AML临床样品中进一步解析DUSP16甲基化与组蛋白H3磷酸化的相关性及临床意义。本项目将揭示新肿瘤抑制基因DUSP16在儿童AML中的功能机制，为儿童AML的防治提供新的理论依据和潜在的干预靶标。

Pediatric acute myeloid leukemia (AML) is one of the most malignant tumors in children. Inactivation of the AML related tumor suppressor genes with promoter hypermethylation is critical for the progress of pediatric AML.We firstly use large sample screening to find that Dual specificity protein phosphatase16 (DUSP16) gene is a new candidate abnormal methylated gene in pediatric AML. Abnormal methylation of DUSP16 is closely related with the prognosis of pediatric AML . Overexpression of DUSP16 gene can promote the apoptosis and G1 cell cycle arrest in AML cells. DUSP16 has the new function of histone H3 dephosphorylation. On the basis of previous research, we are going to confirm whether DUSP16 is tumor suppressor gene related to AML ,focus on studying histone H3 dephosphorylation of DUSP16, reveal the molecular mechanism of abnormal histone H3 phosphorylation regulated by DUSP16 hypermethylation in pediatric AML, clarify the clinical significance of DUSP16 gene methylation and histone H3 phosphorylation in pediatric AML . DUSP16 gene is an important tumor suppressor gene with promoter hypermethylation in pediatric AML, this project will provide new theoretical basis and potential therapeutic targets for the prevention and treatment of pediatric AML.