骨髓增殖性肿瘤(MPN)是由JAK2V617F等基因驱动的慢性肿瘤性疾病，但部分患者易转化为骨髓纤维化或急性白血病，预后极差。因此，深入探索MPN恶性转化的分子机制，有望寻找到MPN疾病进展的核心因素并针对性设计干预措施。本课题组前期应用全基因组筛选、免疫共沉淀及蛋白质谱综合分析发现，JAK2V617F能磷酸化EZH2 SET结构域Y726位点，目前国内外均未见报道。基于已获得的研究结果和MPN临床数据，我们推测JAK2V617F磷酸化修饰的EZH2可能是MPN恶性转化的关键靶点。本研究拟从细胞系、原代细胞、在体模型多方面阐述EZH2磷酸化修饰对MPN进展的影响，并在PRC2依赖性和非依赖性途径上探索可能机制，同时在较大样本中验证EZH2Y726磷酸化与MPN临床特征的相关性。本项目的完成，将有助于明晰MPN进展的关键机制及可能的干预靶标。

Myeloproliferative neoplasms(MPN) is a kind of chronic tumor driven by JAK2V617F. However, some patients are easily converted to myelofibrosis or acute leukemia, and the prognosis is very poor. Therefore, it is important to explore the molecular mechanism of MPN malignant transformation and to design intervention measures. Our previous study showed that JAK2V617F can phosphorylate EZH2 SET domain Y726 sites by whole genome screening, CO-IP analysis and protein mass spectrometry; No reports have been reported at home and abroad. Based on the available results and the clinical data of MPN, we hypothesized that phosphorylation of EZH2 induced by JAK2V617F may be the key target for the malignant transformation of MPN. This study intend to describe the effect of EZH2 phosphorylation by JAK2V617F on the progression of MPN in PRC2 dependent and non dependent pathway, to explore the possible mechanism and correlation between EZH2Y726 phosphorylation and MPN clinical features in a large sample of verification. The completion of this project will help to clarify the key mechanisms of MPN progress and possible intervention targets.