Bonnet D, Dick J E
Department of Genetics, Research Institute, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Nat Med. 1997 Jul;3(7):730-7. doi: 10.1038/nm0797-730.
On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.
关于急性髓系白血病（AML），在造血干细胞层级结构中易发生白血病转化的靶细胞，或者关于表型、基因型和临床异质性的潜在机制方面，几乎没有共识。在此我们证明，在患有严重联合免疫缺陷病的非肥胖糖尿病小鼠（NOD/SCID小鼠）中能够引发人类AML的细胞——称为SCID白血病起始细胞，或SL-IC——具备白血病干细胞所预期的分化、增殖能力以及自我更新潜力。分析的所有AML亚型中的SL-IC，无论白血病母细胞成熟特征的异质性如何，均为CD34++ CD38-，类似于正常SCID重建细胞的细胞表面表型，这表明正常原始细胞而非定向祖细胞是白血病转化的靶细胞。SL-IC能够在体内分化为白血病母细胞，表明白血病克隆是按照层级结构组织的。
