Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia.
Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia.
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DOI：
10.1155/2015/137164
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发表时间：
2015
影响因子：
4.3
通讯作者：
Rieger MA
中科院分区：
文献类型：
--
作者：
Lang F;Wojcik B;Rieger MA
癌症的特征在于显著的肿瘤间、肿瘤内和细胞异质性，这可以通过癌症干细胞（CSC）和/或克隆进化模型来解释。CSC有能力产生肿瘤的所有不同细胞，并在缓解后重新引发疾病。在克隆进化模型中，从单个细胞开始的突变的连续积累导致在线性或分支继承中具有不同适应性的亚克隆的竞争性生长。急性淋巴细胞白血病（ALL）是一种高度恶性的骨髓淋巴系统癌症，复发后预后不良。然而，稳定的表型和功能数据的CSC在ALL，所谓的白血病启动细胞（LIC），是非常有争议的，问题仍然是是否有证据表明它们的存在。本文就B-ALL中LIC的CSC和克隆进化的概念进行了综述，并对LIC分离和评价中的技术争议进行了阐述。这些方面对于发展根除具有LIC能力的细胞的策略是重要的。不同亚克隆中LIC的共同特性需要被定义，以用于未来的ALL诊断、治疗和疾病监测，从而改善ALL患者的预后。
Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients' outcome in ALL.