作者
Liran I Shlush, Sasan Zandi, Amanda Mitchell, Weihsu Claire Chen, Joseph M Brandwein, Vikas Gupta, James A Kennedy, Aaron D Schimmer, Andre C Schuh, Karen W Yee, Jessica L McLeod, Monica Doedens, Jessie JF Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D McPherson, Thomas J Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew MK Brown, Fouad Yousif, Quang M Trinh, Lincoln D Stein, Mark D Minden, Jean CY Wang, John E Dick
发表日期
2014/2/20
期刊
Nature
卷号
506
期号
7488
页码范围
328-333
出版商
Nature Publishing Group UK
简介
In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3Amut) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3Amut-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3Amut arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre …
学术搜索中的文章
LI Shlush, S Zandi, A Mitchell, WC Chen… - Nature, 2014