Modeling the initiation and progression of human acute leukemia in mice
Modeling the initiation and progression of human acute leukemia in mice
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DOI：
10.1126/science.1139851
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发表时间：
2007-04-27
期刊：
影响因子：
56.9
通讯作者：
Dick, John E.
中科院分区：
文献类型：
--
作者：
Barabe, Frederic;Kennedy, James A.;Dick, John E.
我们对白血病的发展和进展的理解一直受到缺乏体内模型的阻碍，在体内模型中疾病是由原代人造血细胞发起的。我们发现，在移植到免疫缺陷小鼠后，表达混合谱系白血病（MLL）融合基因的原始人类造血细胞产生髓系或淋巴系急性白血病，具有重现人类疾病的特征。对连续移植小鼠的分析表明，这种疾病是由白血病起始细胞（l - ic）维持的，这些细胞随着时间的推移从具有种系免疫球蛋白重链（IgH）基因配置的原始细胞类型进化为含有重排的IgH基因的细胞类型。l - ic保留了髓系和淋巴系的潜力，并对微环境线索保持反应。这些细胞的特性为MLL白血病的一些临床特征提供了生物学基础。
Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.