白血病定向诱导分化是肿瘤治疗最为理想的治疗模式。然而，目前除了APL患者外，其它类型白血病缺乏特异性诱导终末分化药物。为此，国内外学者主要致力于不同诱导分化药物的联合诱导方案。本研究在前期创新性的发现小剂量冬凌草甲素与HDAC抑制因子VPA可以协同诱导THP1白血病细胞向单核系定向终末分化后，证实该分化过程TGFβ1/Smad通路发挥主导作用。进一步发现TGFβ1受到上游WT1/Egr-1的竞争性调控，Egr-1则与其组蛋白瓜氨酸或甲基化修饰转变有关。因此，推测PADI4/PRMT2通过表观遗传修饰Egr-1组蛋白，继而引起WT1/Egr-1在TGFβ1启动子上的结合变化，最终导致THP1细胞发生终末分化。该研究重点围绕TGFβ1通路展开上下游关联基因研究，率先揭示上述白血病向单核系终末分化的分子机制。预期在理论上创新单核细胞定向分化信号通路或理论，为白血病治疗提供新的靶点。

The committed differentiation of leukemia is the ideal mode of treatment for tumor treatment. However, only patients with APL could be induced to get complete remission. Other types of leukemia cannot get clinical remission because it cannot be induced into terminal differentiation. For the lack of specific induction drugs, the other types of leukemia mainly dedicated to different combinations of differentiation-inducing agents. In the present study, the THP1 cell line was taken as a mode to induce terminal differentiation of THP1 cells by combination of low concentration oridonin and VPA, and the expression of TGFβ1/Smad,WT1/Egr-1,PADI4 and PRMT was related to each other in the process of differentiation. We speculate that the switch of PADI4 to PRMT2 binding on promoter of Egr-1 could induce the variation of WT1 to Egr1 binding on promoter of TGFβ1,which results in the terminal differentiation of THP1.