Mariani Samanta A, Calabretta Bruno
Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, United States.
Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, United States.
Mol Aspects Med. 2014 Oct;39:102-9. doi: 10.1016/j.mam.2013.06.003. Epub 2013 Jun 29.
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 behavior 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.
髓系白血病在形态学、免疫表型、遗传和表观遗传学改变以及对治疗的反应方面都是异质性恶性肿瘤。这种异质性被认为取决于继发性突变的积累，这些突变增强了一小部分能够自我更新的白血病起始细胞的增殖/存活能力和/或阻断了其分化。这种克隆进化模型基于异种移植研究，该研究表明，一小部分免疫表型与正常造血干细胞相似的纯化白血病细胞能够在免疫缺陷小鼠中引发并维持白血病，这就是所谓的白血病干细胞模型。自该模型最初提出以来，许多研究都证实了这一模型的主要结论。然而，最近在免疫缺陷更严重的小鼠中进行的异种移植研究数据表明，白血病干细胞的免疫表型和行为比最初认为的更加异质和“可塑性”。我们将在此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。
