Biology of normal and acute myeloid leukemia stem cells
Biology of normal and acute myeloid leukemia stem cells
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DOI：
10.1532/ijh97.05144
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发表时间：
2005-12-01
影响因子：
2.1
通讯作者：
Lapidot, T
中科院分区：
文献类型：
--
作者：
Dick, JE;Lapidot, T
在过去的50年中，对血液形成生物学的实质性理解主要是由于对从多能干细胞到成熟细胞的所有分化阶段的细胞的功能定量测定的发展。大多数研究涉及小鼠，因为用这种动物模型进行再增殖研究的容易性允许测定干细胞的完整谱系发育。在过去的十年中，在使用异种移植的人类干细胞再增殖试验的进展，大大提高了我们对人类干细胞生物学的理解。重要的是，异种移植方法也被用于鉴定启动和维持白血病增殖的癌症干细胞，为癌症干细胞假说提供了关键证据。这种假说认为，癌细胞在功能上是异质的，并且是分层组织的，使得只有特定的细胞能够维持肿瘤生长并持续产生构成肿瘤主体的细胞。最近的研究也使人们关注干细胞（正常或白血病）与其微环境之间的密切关系的重要性。进入视野的是参与干细胞归巢、迁移和粘附的分子，以及微环境生态位的细胞组分。在这里，我们回顾了最近的研究，已经开始阐明正常和白血病的人类干细胞和他们的微环境之间的相互作用。
The substantial understanding that has been gained over the past 5 decades of the biology of blood formation is largely due to the development of functional quantitative assays for cells at all stages of differentiation, from multipotential stem cells to mature cells. The majority of studies have involved the mouse because the ease with which repopulation studies can be carried out with this animal model allows the assay of complete lineage development from stem cells. In the past decade, advances in repopulation assays for human stem cells using xenotransplantation have greatly enhanced our understanding of human stem cell biology. Importantly, the xenotransplantation methodology has also been used to identify the cancer stem cell that initiates and sustains leukemic proliferation, providing key evidence for the cancer stem cell hypothesis. This hypothesis argues that cancer cells are functionally heterogeneous and hierarchically organized such that only specific cells are capable of sustaining tumor growth and continuously producing the cells that make up the bulk of the tumor. Recent studies have also brought into focus the importance of the intimate relationship between the stem cell (normal or leukemic) and its inicroenvironment. Coming into view are the molecular players involved in stem cell homing, migration, and adhesion, as well as the cellular components of the microenvironmental niche. Here we review recent studies that have begun to elucidate the interplay between normal and leukemic human stem cells and their microenvironment.