苯造血毒性防治重点在于阐明机制和寻找早期标志物。课题组前期研究发现STAT3低甲基化参与调控苯的造血毒性，但机制不清。TET2作为DNA甲基化的重要调节因子，是调控造血的重要蛋白，提示TET2可能是苯造血毒性的关键分子，通过介导STAT3低甲基化调控造血干/祖细胞的更新分化，继而导致苯的造血毒性。近期课题组成功建立了人源造血干/祖细胞的培养体系，本项目拟以此为基础利用高内涵、PCR荧光探针、测序、甲基化PCR、RNAi等方法研究苯代谢物1,4-苯醌致造血干/祖细胞更新分化异常中TET2表达、STAT3甲基化的变化规律及TET2介导STAT3低甲基化在造血干/祖细胞更新分化异常中的作用；在已建立的苯职业人群队列中分析苯暴露，TET2、STAT3表达和血象之间的相关性及量效关系。阐明TET2调控STAT3低甲基化在苯造血毒性中的作用和机制，探索将TET2用于苯接触人群造血危害早期筛查的新靶点。

Prevention and treatment of hematopoietic toxicity focus on elucidating the mechanism and looking for early biomarkers. Our previous reports found that Signal Transducer and Activator of Transcription 3 (STAT3) hypomethylation participated in benzene hematopoietic toxicity, but the mechanism was still unclear. Ten-eleven translocation 2 (TET2), as hematopoiesis regulation proteins, can regulate DNA demethylation by hydroxylating 5-methylcytosine to 5-hydroxymethylcytosine. Therefore, we hypothesize that TET2 may be a key molecule of benzene hematopoietic toxicity, through mediating STAT3 methylation to regulate the renewal and differentiation of hematopoietic stem/progenitor cell, resulting in hematopoietic toxicity of benzene. Our group has been successfully established defined culture conditions for directing human induced pluripotent stem cells differentiation toward human hematopoietic stem/progenitor cells (hHSPCs). In order to reveal the effect and mechanism of STAT3 hypomethylation mediated by TET2 involved in benzene hematopoietic toxicity, the research was designed to explore the regularity of TET2 expression and STAT3 hypomethylation and to monitor the renewal and differentiation of hHSPCs disturbed by 1,4-BQ using high content screening (HCS), PCR-fluorescence probe, sequencing, methylation-specific PCR and RNAi. The correlations and dose-effect relationships of benzene exposure, the relative expression of TET2 and STAT3 and hemogram were analyzed based on a cohort of benzene exposure population. Taken together, this study is to clarify the effect and mechanism of STAT3 hypomethylation mediated by TET2 involved in benzene hematopoietic toxicity and to verify that TET2 may be a new potential target for early screening in population exposed to benzene.