Nature:科学家发现诱发急性髓性白血病的干细胞

Nature:科学家发现诱发急性髓性白血病的干细胞
[size=1.1em]作者：[size=1.1em]墨涂涂[size=1.1em]来源：[size=1.1em]生物谷  关键词： 干细胞 急性髓性白血病 DNMT3a

                               
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2014年2月14日 讯 /生物谷BIOON/ --干细胞学家John Dick领导的研究团队近日发现白血病前干细胞（pre-leukemic stem cells）能够诱发急性髓性白血病（acute myeloid leukemia，AML），同时也会引起病人治疗后的复发。相关报道发表在近期的Nature杂志上。

Dick博士是多伦多大学分子遗传学系的教授，他是癌症干细胞领域的先驱，早在1994年，Dick博士首先鉴定出了白血病干细胞，并在2007年成功克隆了癌症干细胞。

Dick博士称，该发现揭示了急性髓性白血病的发病原因之一，鉴定哪些病人是因白血病前干细胞而发病是个性化癌症治疗的第一步。在发病进程中，越早期发现白血病前干细胞，并对其进行干预，治疗的效果会越好。

科学家发现在25%的AML病人中有DNMT3a基因突变，而该基因突变导致造血干细胞异常生长，产生白血病前干细胞。而这些存在于骨髓的干细胞在化疗过程中不能被杀死，所以会导致病人在化疗后产生复发现象。

Dick博士称，人们认为AML复发是由于化疗并没有完全杀死癌细胞导致的，我们的研究表明虽然有些情况确实是这样，但是有些情况是由于白血病前干细胞异常生长，导致疾病的再次发展。（生物谷Bioon.com）

                               
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doi:10.1038/nature13038

Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia

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 J. F. Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D. McPherson, Thomas J. Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew M. K. Brown, Quang M. Trinh, Lincoln D. Stein, Mark D. Minden, Jean C. Y. Wang, John E. Dick

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-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.

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