Somervaille Tim C P, Cleary Michael L
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Cancer Cell. 2006 Oct;10(4):257-68. doi: 10.1016/j.ccr.2006.08.020.
Using a mouse model of human acute myeloid leukemia (AML) induced by the MLL-AF9 oncogene, we demonstrate that colony-forming cells (CFCs) in the bone marrow and spleen of leukemic mice are also leukemia stem cells (LSCs). These self-renewing cells (1) are frequent, accounting for 25%-30% of myeloid lineage cells at late-stage disease; (2) generate a phenotypic, morphologic, and functional leukemia cell hierarchy; (3) express mature myeloid lineage-specific antigens; and (4) exhibit altered microenvironmental interactions by comparison with the oncogene-immortalized CFCs that initiated the disease. Therefore, the LSCs responsible for sustaining, expanding, and regenerating MLL-AF9 AML are downstream myeloid lineage cells, which have acquired an aberrant Hox-associated self-renewal program as well as other biologic features of hematopoietic stem cells.
利用由MLL-AF9致癌基因诱导的人类急性髓系白血病（AML）小鼠模型，我们证明白血病小鼠骨髓和脾脏中的集落形成细胞（CFC）也是白血病干细胞（LSC）。这些自我更新细胞具有以下特点：（1）数量较多，在疾病晚期占髓系细胞的25%-30%；（2）产生具有表型、形态和功能的白血病细胞层级结构；（3）表达成熟髓系特异性抗原；（4）与引发疾病的致癌基因永生化CFC相比，其与微环境的相互作用发生了改变。因此，负责维持、扩增和再生MLL-AF9 AML的LSC是下游髓系细胞，它们获得了异常的Hox相关自我更新程序以及造血干细胞的其他生物学特征。
