Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity

被引：732

作者：

Hope, KJ

Jin, LQ

Dick, JE

机构：

[1] Univ Toronto, Univ Hlth Network, Div Cell & Mol Biol, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Mol Genet & Microbiol, Toronto, ON M5G 2C1, Canada

来源：

NATURE IMMUNOLOGY | 2004年 / 5卷 / 07期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1038/ni1080

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Emerging evidence suggests cancer stem cells sustain neoplasms; however, little is understood of the normal cell initially targeted and the resultant cancer stem cells. We show here, by tracking individual human leukemia stem cells (LSCs) in nonobese diabetic-severe combined immunodeficiency mice serially transplanted with acute myeloid leukemia cells, that LSCs are not functionally homogeneous but, like the normal hematopoietic stem cell (HSC) compartment, comprise distinct hierarchically arranged LSC classes. Distinct LSC fates derived from heterogeneous self-renewal potential. Some LSCs emerged only in recipients of serial transplantation, indicating they divided rarely and underwent self-renewal rather than commitment after cell division within primary recipients. Heterogeneity in LSC self-renewal potential supports the hypothesis that they derive from normal HSCs. Furthermore, normal developmental processes are not completely abolished during leukemogenesis. The existence of multiple stem cell classes shows the need for LSC-targeted therapies.

引用

页码：738 / 743

页数：6

共 39 条

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