骨髓增殖性肿瘤动物模型和药物研发进展

Advances on animal models and drug development of myeloproliferation neoplasms

骨髓增殖性肿瘤(myeloproliferative neoplasm,MPN)是临床上骨髓髓系细胞异常增生和进行性骨髓纤维化为特征的克隆性造血功能障碍疾病。费城阴性MPNs主要包括真性红细胞增多症、原发性血小板增多症和骨髓纤维化。基于其复杂的发病机制,目前已成功创建转染突变基因细胞移植、转基因和基因敲入等几种相关动物模型,以及Janus激酶2抑制剂、端粒酶抑制剂、雷帕霉素靶蛋白抑制剂、组蛋白脱乙酰胺酶抑制剂、腺苷酸活化的蛋白激酶激动剂等多靶点的药物研究。本文对近年来MPNs发病机制、相关动物模型和药物研究进展做一综述,旨在为抗MPNs新药研究提供新思路。

Myeloproliferation neoplasms(MPNs)are a kind of disease of clonal hematopoietic dysfunction clinically characterized by abnormal proliferation of bone marrow myeloid cells and progressive myelofibrosis.The Philadelphia-negative MPNs mainly include polycythemia vera,essential thrombocythemia and myelofibrosis.Based on its complex pathogenesis,several related animal models have been successfully created,such as of mutant gene transplantation model,transgenic model and gene knock-in model.Multiple-target drug research were conducted such as Janus kinase 2 inhibitor,telomerase inhibitor,mTOR inhibitor,HDACs inhibitor,and AMP-activated kinase excit agent.The article reviews the pathogenesis of MPNs,related animal models and drug research progress in recent years,providing novel ideas for the research of new therapeutic drug against MPNs.