中山大学学报（自然科学版）（中英文）2025，Vol.64Issue(3)：47-59,13.DOI:10.13471/j.cnki.acta.snus.ZR20240274
c-Mpl新型剪切体c-Mpl-D在急性髓系白血病中的表达与功能
Expression and functional analysis of the novel c-Mpl splice variant c-Mpl-D in acute myeloid leukemia
摘要
Abstract
Thrombopoietin(TPO)regulates the development of megakaryocytes and the production of platelets through its receptor c-Mpl,and has a negative correlation with the prognosis and survival of various tumors,which is related to the internalization and degradation of circulating TPO and the endocytosis of the c-Mpl splice variant c-Mpl-D.This study constructed a UT-7/c-Mpl-D stable cell line using a reverse transcription expression system to study the function of c-Mpl-D in isolation.A Dami/c-Mpl-D stable cell line was also constructed by electroporation to investigate the regulatory effect of c-Mpl-D on c-Mpl-F function.Further,the interaction between c-Mpl-D and TPO was studied using crosslinking and immunoprecipitation.The results indicated that,when coexisting with c-Mpl-F,c-Mpl-D can promote Dami cell proliferation,inhibit Dami cell apoptosis,and prevent Dami cells from maturing towards megakaryocytes.Additionally,c-Mpl-D significantly reduced the receptor internalization effect after TPO stimulation.In summary,this study proposes a model related to the physiological significance of the increasing expression of c-Mpl-D with the differentiation and maturation of megakaryocytes,providing new insights into the relationship between c-Mpl-D and the proliferation and differentiation of megakaryocytes.It offers new experimental evidences for the analysis of the mechanisms of megakaryocyte proliferation and differentiation,and promotes the prevention,diagnosis,and treatment of c-Mpl-D-related diseases.关键词
c-Mpl-D/巨核细胞/增殖/分化/内化Key words
c-Mpl-D/megakaryocytes/proliferation/differentiation/internalization分类
生物学引用本文复制引用
王家胜,范加希,王淇,黄萱,陈伟庭,张擎,李飞,何越,吴乐燕,李春谋,曾茂桢,陈俊汝,陈海生,郭琪琪..c-Mpl新型剪切体c-Mpl-D在急性髓系白血病中的表达与功能[J].中山大学学报（自然科学版）（中英文）,2025,64(3):47-59,13.基金项目
国家自然科学基金(82273467) （82273467）
嘉应学院人才启动项目(323E0467) （323E0467）
深圳市科技创新委员会基础研究计划(JCYJ20210324120812035) （JCYJ20210324120812035）
中山大学中央高校基本科研业务费(24qnpy180) （24qnpy180）
