Leukemia stem cells: Old concepts and new perspectives.
Leukemia stem cells: Old concepts and new perspectives.
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DOI：
10.1016/j.mam.2013.06.003
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发表时间：
2014-10
影响因子：
10.6
通讯作者：
Calabretta B
中科院分区：
文献类型：
--
作者：
Mariani SA;Calabretta B
髓系白血病是一种在形态、免疫表型、遗传和表观遗传学改变以及治疗反应方面的异质性恶性肿瘤。这种异质性被认为依赖于次级突变的积累，增强了白血病启动细胞的增殖/存活和/或阻止分化，使其能够自我更新。这一克隆进化模型是基于异种移植研究，该研究表明，在免疫缺陷小鼠中，白血病可以由一小部分纯化的白血病细胞启动和维持，其免疫表型与正常造血干细胞相似，被称为白血病干细胞模型。自其最初提出以来，许多研究都验证了该模型的主要结论。然而，最近在更严重的免疫缺陷小鼠身上进行的异种移植研究的数据表明，白血病干细胞的免疫表型和行为比最初认为的更加异质性和“可塑性”。我们将在这里讨论白血病干细胞模型的演变及其对髓系恶性肿瘤患者治疗的影响。
Myeloid leukemias are heterogeneous malignancies in morphology, immunophenotype, genetic and epigenetic alterations, and response to therapy. This heterogeneity is thought to depend on the accumulation of secondary mutations enhancing proliferation/survival and/or blocking differentiation in a small subset of leukemia-initiating cells capable of self-renewal. This model of clonal evolution is based on xenotransplantation studies demonstrating that leukemia can be initiated and maintained in immunodeficient mice by a small subset of purified leukemic cells immunophenotypically similar to normal hematopoietic stem cells and is known as the leukemia stem cell model. Since its original formulation, many studies have validated the main conclusion of this model. However, recent data from xenotransplantation studies in more severely immunodeficient mice suggest that imunophenotype and behaviour of leukemic stem cells is more heterogeneous and “plastic” than originally thought. We will discuss here the evolution of the leukemia stem cell model and its impact for the therapy of patients with myeloid malignancies.
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