原发性骨髓纤维化（Primary Myelofibrosis, PMF）是一种起源于造血干细胞的克隆性疾病。PMF患者临床症状明显，生活质量差，向白血病转化风险高，生存期短。目前尚缺乏能够有效改善PMF疾病进程的药物。我们此前系列研究发现我国PMF患者具有有别于西方国家白种人PMF患者的独特临床表现、分子生物学和细胞遗传学特征。本课题在这些前期原创性研究发现的基础上得以提出，旨在明确我国PMF患者基因突变谱系和克隆演变规律，初步阐释不同的启动基因突变和亚克隆基因突变组合在PMF发生和演变中作用及其分子机制，并模拟患者体内基因突变特征构建新的转基因PMF小鼠模型，以及从传统中草药的单体成分中寻找治疗PMF的新药并探讨其可能的分子药理机制。

Primary myelofibrosis （PMF）is a clonal disease derived from hematopoetic stem cell. Patients with PMF have obvious symptoms, poor quality of life, high risk of leukemia transformation and brief survival. There is no efficient drug which alters the natural history of PMF. Our previous studies showed that Chinese patients with PMF have unique features of clinical symptoms, molecular biology and cytogenetics compared with predominately white patients. Based on our findings, the spectrum of gene mutations and clonal evolution and molecular mechanisms of various driver mutations and subclonal mutations in Chinese patients with PMF will be explored. Some new mouse models which have similar molecular characteristics to patients will be developed. In addition，antifibrotic mechanisms of active ingredient from Chinese herb will be explored.