SENP1在c-Myb参与的急性髓细胞白血病中的作用与分子机制

SENP1 mediated SUMO modification, how to regulate c-Myb participation incidence of acute myelocytic leukemia（AML）is a important scientific issues. Our previous study found that c-Myb play a role in ES cell hematopoietic differentiation/transformation, the expression of SENP1 and c-myb were related in AML bone marrow, the expression of SENP1 and c-myb decreased down synchronization in AML cell lines of induced to differentiation. The literature suggests that SENP1 regulation of Elk1 gene associated with leukemia, There is one potential Elkl binding site in the sequence of the c-myb promoter region.Therefore, we speculated that SENP1-mediated SUMO modification may be associated with c-Myb and Elk1 in AML. The hypothesis is that SENP1 mediated SUMO modification direct regulated c-myb or indirect regulaed c-myb by Elk1 in AML. This project intends to establish AML cell lines of SENP1 knockout cell model, in order to understand how the interaction and mechanism of SENP1, c-Myb and Elk1 by the specimens and cell line of AML. It will be confirmation in SENP1 knockout mouse model. The findings have great significance involved in AML of molecular mechanisms for the to clarify SENP1 regulation of c-Myb.

SENP1介导SUMO修饰如何调节c-Myb参与AML发病，是白血病发病机制中重要的科学问题。我们前期研究发现c-Myb在ES细胞造血分化/转化中均发挥作用；AML骨髓中SENP1和c-Myb的高表达存在相关性；AML细胞系诱导分化后SENP1与c-Myb表达同步下调。文献提示SENP1调控Elk1基因与白血病相关，c-myb启动子区域有Elk1结合位点。因此我们推测在AML中SENP1介导SUMO修饰可能与c-Myb及Elk1相关，提出SENP1介导SUMO修饰调控c-Myb或经Elk1间接调控c-Myb参与AML发病的假说。本课题拟建立AML细胞系SENP1敲低细胞模型，在AML标本及细胞水平研究SENP1与c-Myb及Elk1对细胞分化与生物学功能的影响及其机制，并利用SENP1敲出小鼠模型进行验证。研究结果对于阐明SENP1调控c-Myb参与AML发病的分子机制具有十分重要的意义。