Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34− fraction

Author:

Taussig David C.12,Vargaftig Jacques2,Miraki-Moud Farideh1,Griessinger Emmanuel2,Sharrock Kirsty3,Luke Tina3,Lillington Debra1,Oakervee Heather1,Cavenagh Jamie1,Agrawal Samir G.1,Lister T. Andrew1,Gribben John G.1,Bonnet Dominique2

Affiliation:

1. Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, Queen Mary University of London, London; and

2. Haematopoietic Stem Cell Laboratory and

3. FACS Laboratory, Cancer Research UK London Research Institute, London, United Kingdom

Abstract

Abstract Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34+ fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34+ fraction. We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately one-half of cases had LICs exclusively within the CD34− fraction, whereas the CD34+ fraction contained normal multilineage hematopoietic repopulating cells. Most of the remaining cases had LICs in both CD34+ and CD34− fractions. When samples were sorted based on CD34 and CD38 expression, multiple fractions initiated leukemia in primary and secondary recipients. The data indicate that the phenotype of LICs is more heterogeneous than previously realized and can vary even within a single sample. This feature of LICs may make them particularly difficult to eradicate using therapies targeted against surface antigens.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Cited by 306 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3