Cui Jiu-Wei, Zhang Xue-Min, Wang Guan-Jun
Department of Hematology, the First Clinical Hospital of Jilin University, Changchun 130021, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2003 Oct;11(5):549-52.
Acute myelogenous leukemia (AML) cells are organized in a hierarchical fashion, with only the most primitive rare population (leukemia stem cell, LSC) of AML cells capable of maintaining the leukemic clone. A broad range of studies has indicated that AML results from mutations at the level of the stem cells of AML cells. The changes of cellular and molecular features in these malignant stem cells determine the features of leukemic clone and give rise to different subtypes of AML. LSCs share some similar characteristics with normal hematopoietic stem cells (HSC) including the ability to self-renew, and also have the potential of limited differentiation. LSCs, also have some features that are not found in normal HSC. LSCs have unique phenotype such as CD90-, CD117- and CD123+. Tumor-suppressor protein-death associated protein kinase and interferon regulatory factor 1 were overexpressed in LSCs, but not in normal HSC. Due to a predominantly G0 cell-cycle status, LSCs may not be responsive to conventional chemotherapeutic agents, compared with leukemia blasts. It is proposed that surviving LSCs are a major contributing factor to leukemic relapse. Although LSC population is likely to be drug-resistant, quiescent LSCs are preferentially susceptible to apoptosis induction while sparing normal HSC, with the appropriate stimulus such as proteasome inhibitor MG-132. This article reviewed the data emerging from the study of LSCs, and elucidated the distinct cellular and molecular characteristics of the LSC population, which may shed new light on AML therapy and leukemogenesis study.
急性髓系白血病（AML）细胞呈层级式组织，只有最原始的稀有细胞群（白血病干细胞，LSC）能够维持白血病克隆。大量研究表明，AML源于AML细胞干细胞水平的突变。这些恶性干细胞中细胞和分子特征的变化决定了白血病克隆的特征，并产生不同亚型的AML。LSC与正常造血干细胞（HSC）具有一些相似特征，包括自我更新能力，也具有有限分化的潜力。LSC也具有一些正常HSC中未发现的特征。LSC具有独特的表型，如CD90 -、CD117 -和CD123 +。肿瘤抑制蛋白——死亡相关蛋白激酶和干扰素调节因子1在LSC中过表达，但在正常HSC中不表达。由于主要处于G0细胞周期状态，与白血病原始细胞相比，LSC可能对传统化疗药物无反应。有人提出，存活的LSC是白血病复发的主要因素。尽管LSC群体可能具有耐药性，但静止的LSC在受到适当刺激（如蛋白酶体抑制剂MG - 132）时，优先易于被诱导凋亡，同时使正常HSC免受影响。本文综述了LSC研究中出现的数据，并阐明了LSC群体独特的细胞和分子特征，这可能为AML治疗和白血病发生机制研究提供新的线索。
