我重点实验室程涛课题组在Blood期刊发表文章“Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation


   Cytopenias resulting from the impaired generation of normal blood cells from hematopoietic precursors are important contributors to morbidity and mortality in patients with leukemia. However, the process by which normal hematopoietic cells are overtaken by emerging leukemia cells and how different subsets of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) are distinctly influenced during leukemic cell infiltration is poorly understood. To investigate these important questions, we used a robust non-irradiated mouse model of human MLL-AF9 leukemia to examine the suppression of HSCs and HPCs during leukemia cell expansion in vivo. Among all the hematopoietic subsets, long-term repopulating HSCs were the least reduced whereas megakaryocytic-erythroid progenitors (MEPs) were the most significantly suppressed. Notably, nearly all of HSCs were forced into a non-cycling state in leukemic marrow at late stages, but their reconstitution potential appeared to be intact upon transplantation into non-leukemic hosts. Gene expression profiling and further functional validation revealed that Egr3 was a strong limiting factor for the proliferative potential of HSCs. Therefore, this study provides not only a molecular basis for the more tightened quiescence of HSCs in leukemia but also a novel approach for defining functional regulators of HSCs in disease.


网站导航 | 联系我们 | 使用帮助 | 网站声明

主办:中国医学科学院血液学研究所血液病医院  技术支持:北方网

友情链接:线上快三投注平台  快3网上投注平台  快3网上投注平台  快三在线投注平台  快3网  

免责声明: 本站资料及图片来源互联网文章,本网不承担任何由内容信息所引起的争议和法律责任。所有作品版权归原创作者所有,与本站立场无关,如用户分享不慎侵犯了您的权益,请联系我们告知,我们将做删除处理!