Hematology Division, Department of Internal Medicine, Medical School of Ribeirão Preto and National Institute of Science and Technology on Cell Based Therapy, University of São Paulo, Campus USP, Ribeirão Preto, SP, Brazil.
Anticancer Agents Med Chem. 2010 Feb;10(2):104-10. doi: 10.2174/187152010790909281.
The idea that within the bulk of leukemic cells there are immature progenitors which are intrinsically resistant to chemotherapy and able to repopulate the tumor after treatment is not recent. Nevertheless, the term leukemia stem cells (LSCs) has been adopted recently to describe these immature progenitors based on the fact that they share the most relevant features of the normal hematopoetic stem cells (HSCs), i.e. the self-renewal potential and quiescent status. LSCs differ from their normal counterparts and from the more differentiated leukemic cells regarding the default status of pathways regulating apoptosis, cell cycle, telomere maintenance and transport pumps activity. In addition, unique features regarding the interaction of these cells with the microenvironment have been characterized. Therapeutic strategies targeting these unique features are at different stages of development but the reported results are promising. The aim of this review is, by taking acute myeloid leukemia (AML) as a bona fide example, to discuss some of the mechanisms used by the LSCs to survive and the strategies which could be used to eradicate these cells.
白血病细胞内存在对化疗具有内在抗性且能够在治疗后重新填充肿瘤的不成熟祖细胞，这种观点并非最近才出现。然而，基于这些不成熟祖细胞与正常造血干细胞（HSCs）具有最相关的特征，即自我更新能力和静止状态，最近采用了白血病干细胞（LSCs）这一术语来描述它们。LSCs 在调节凋亡、细胞周期、端粒维持和转运泵活性的途径的默认状态方面与正常细胞和更分化的白血病细胞不同。此外，还对这些细胞与微环境相互作用的独特特征进行了表征。针对这些独特特征的治疗策略处于不同的开发阶段，但报告的结果是有希望的。本综述的目的是通过以急性髓细胞白血病（AML）为例，讨论 LSCs 用于存活的一些机制以及可用于根除这些细胞的策略。
