Leukemia stem cells
Leukemia stem cells
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DOI：
10.1002/ijc.26318
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发表时间：
2011-11-15
影响因子：
6.4
通讯作者：
Ho, Anthony D.
中科院分区：
文献类型：
--
作者：
Buss, Eike C.;Ho, Anthony D.
白血病干细胞（LSC）可能来源于正常造血干细胞（HSC）的恶性转化，或者来源于其中获得性突变重新安装了失调的自我更新程序的祖细胞。LSC处于层次结构的顶部，并产生具有更多分化特征的白血病细胞。虽然大多数白血病细胞最初对化疗和放疗敏感，但LSC具有耐药性，并被认为是初始反应后疾病复发的基础。尽管已经从将人白血病细胞引入免疫缺陷小鼠模型的异种移植模型中获得了关于LSC生物学的重要知识，但是人LSC候选物的前瞻性鉴定和分离仍然难以捉摸，并且其预后和治疗意义存在争议。本文综述了急性髓系白血病（AML）患者来源的人LSC的鉴定、富集和表征。将总结证明估计LSC负荷和消除LSC策略的临床意义的实验数据。对于AML的长期治愈，重要的是定义LSC候选者并了解其与正常HSC相比的肿瘤生物学。这种比较研究可能为识别LSC和制定可能能够根除它们的治疗策略提供新的标志物。
Leukemia stem cells (LSCs) might originate from malignant transformation of normal hematopoietic stem cells (HSCs), or alternatively, of progenitors in which the acquired mutations have re-installed a dysregulated self-renewal program. LSCs are on top of a hierarchy and generate leukemia cells with more differentiated characteristics. While most leukemia cells are initially sensitive to chemo-and radiotherapy, LSCs are resistant and are considered to be the basis for disease relapse after initial response. Albeit important knowledge on LSC biology has been gained from xenogeneic transplantation models introducing human leukemia cells into immune deficient mouse models, the prospective identification and isolation of human LSC candidates has remained elusive and their prognostic and therapeutic significance controversial. This review focuses on the identification, enrichment and characterization of human LSC derived from patients with acute myeloid leukemia (AML). Experimental data demonstrating the clinical significance of estimating LSC burden and strategies to eliminate LSC will be summarized. For long-term cure of AML, it is of importance to define LSC candidates and to understand their tumor biology compared to normal HSCs. Such comparative studies might provide novel markers for the identification of LSC and for the development of treatment strategies that might be able to eradicate them.