Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia
Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia
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DOI：
10.1016/j.ccr.2006.08.020
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发表时间：
2006-10-01
期刊：
影响因子：
50.3
通讯作者：
Cleary, Michael L.
中科院分区：
文献类型：
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作者：
Somervaille, Tim C. P.;Cleary, Michael L.
使用MLL-AF 9癌基因诱导的人急性髓性白血病（AML）小鼠模型，我们证明了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）。这些自我更新的细胞（1）是常见的，占疾病晚期髓系细胞的25%-30%;（2）产生表型，形态学和功能性白血病细胞等级;（3）表达成熟的髓系特异性抗原;（4）与引发疾病的癌基因永生化CFC相比，表现出改变的微环境相互作用。因此，负责维持、扩增和再生MLL-AF 9 AML的LSC是下游髓系细胞，其已获得异常的Hox相关自我更新程序以及造血干细胞的其他生物学特征。
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.