Cancer stem cells and the cellular hierarchy in haematological malignancies.
Cancer stem cells and the cellular hierarchy in haematological malignancies.
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DOI：
10.1016/s0959-8049(09)70033-4
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发表时间：
2009-09-01
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影响因子：
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通讯作者：
Dybkaer, Karen
中科院分区：
文献类型：
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作者：
Johnsen, Hans Erik;Kjeldsen, Malene Krag;Dybkaer, Karen
造血系统中的恶性肿瘤似乎依赖于一小部分所谓的癌症干细胞（CSC）的持续生长和进展-这首先被描述为白血病的“睡眠-饲养理论”。白血病干细胞是第一个被描述的亚群，尽管这些细胞的起源一直难以解剖。因此，它们的生物学尚未完全阐明，这也适用于正常组织对应物。干细胞概念描述了干细胞是低频率的，自我更新的，并具有基于现象学的多谱系潜力-当在动物和人类体内和体外研究时，该定义可能不严格适用于CSC。几项研究分析了造血系统的细胞分级，通过对少数甚至单个细胞进行细胞分选，跟踪获得的遗传变化，并进行移植模型研究，以记录分化分级中的子集作为潜在的CSC区室。在白血病中，CSC被描述为存在于造血干细胞（HSC）的骨髓室中;然而，在其他骨髓疾病如多发性骨髓瘤中，起源细胞可能是分化程度更高的细胞，如生殖后记忆B细胞或浆母细胞。迄今为止进行的研究甚至表明，遗传事件可能发生在不同的B细胞亚群中，与疾病的逐步肿瘤发生一致。虽然我们对这些起始细胞的性质和生物学的理解仍然是未知的，但这些细胞的明显存在对于理解初始恶性转化和疾病转移或进展以及最重要的是，针对具有CSC功能的子集选择个性化治疗策略具有意义。在目前的审查干细胞在血液系统恶性肿瘤，我们集中在两个主题，第一，描述干细胞的概念在健康和疾病，其“现象学”，第二，描述CSC车厢白血病和多发性骨髓瘤。
Malignancies in the haematopoietic system seem to depend on a small subset of so-called cancer stem cells (CSC) for their continued growth and progression - this was first described as the "sleeper-feeder theory" for leukaemia. The leukaemia stem cell was the first of such subsets to be described although the origins of these cells have been difficult to dissect. Consequently, their biology is not fully elucidated, which also holds true for the normal-tissue counterparts. The stem cell concept describes stem cells to be of low frequency, self renewing and with multilineage potential based on phenomenology - a definition which may not hold strictly true for CSCs when studied in animals and humans in vivo and in vitro. Several studies have analysed the cellular hierarchy of the haematopoietic system by cell sorting of few and even single cells, tracking acquired genetic changes and performing transplantation model studies to document subsets within the differentiating hierarchy as potential CSC compartments. In leukaemia the CSC has been described in the bone marrow compartment of haematopoietic stem cells (HSC); however, in other bone marrow disorders like multiple myeloma it is likely that the cell of origin is a more differentiated cell, like post-germinal memory B cells or plasmablasts. Studies performed so far have even indicated that the genetic events may occur in different B cell subsets in accordance with the stepwise oncogenesis of the disease. Although our understanding of the nature and biology of these initiating cells remains unknown, the obvious existence of such cells has implications for understanding initial malignant transformation and disease metastasis or progression and, most important, the selection of individualised therapeutic strategies targeting the subsets harbouring the CSC function. In the present review on stem cells in haematological malignancies we have focused on two topics, first, describing the stem cell concept in health and disease, and its "phenomenology", and second, describing the CSC compartments in leukaemia and multiple myeloma.