脾脏CD45-Ter119+细胞在幼年型粒单核细胞白血病发生发展中的作用及机制研究

脾脏肿大是幼年型粒单核细胞白血病（JMML）重要的诊断依据，但是，其在JMML中的作用尚不清楚，肿大脾脏中CD45-Ter119+细胞能够促进肿瘤的发展。我们在JMML小鼠模型的脾脏中发现CD45-Ter119+细胞比例增多且花生四烯酸含量显著升高，同时花生四烯酸代谢相关的基因Cyp2s1等在造血干祖细胞（HSPC）中表达上升。由此我们推测脾脏CD45-Ter119+细胞可能通过花生四烯酸代谢调控了JMML的发生发展。因此本项目拟首先利用外周血检测、生存曲线分析和造血系统分析阐明脾脏CD45-Ter119+细胞对幼年型粒单核细胞白血病的影响，然后通过细胞周期和集落形成实验解析花生四烯酸对HSPC功能的影响，最后利用蛋白磷酸化流式分析和转录组测序等技术挖掘其调控机制。本项目将为幼年型粒单核细胞白血病的治疗提供理论依据。

Splenomegaly is an important diagnostic basis for juvenile myelomonocytic leukemia (JMML), however, its role in JMML remains unclear. Recent studies had shown that splenic CD45-Ter119+ cells can promote cancer progression. In the spleen of JMML mouse model, we found that the proportion of CD45-Ter119+ cells increased and arachidonic acid content elevated significantly. Meanwhile, the expression of arachidonic acid metabolism-related gene such as Cyp2s1 raised in hematopoietic stem and progenitor cells (HSPC). So we hypothesize that splenic CD45-Ter119+ cells may regulate progression of JMML through arachidonic acid.Therefore, in this project, the influence of splenic CD45-Ter119+ cells on IMML is firstly clarified by peripheral blood test, survival curve analysis and hematopoietic system analysis, and then the influence of arachidonic acid on HSPC function is analyzed by cell cycle and colony formating experiments in vivo. Finally, the regulation mechanism is explored by protein phosphorylation flow analysis and transcriptome sequencing. This project will provide theoretical basis for the treatment of JMML.