Miyamoto T, Weissman I L, Akashi K
Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7521-6. doi: 10.1073/pnas.97.13.7521.
Leukemia-specific AML1/ETO transcripts are detectable in most patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. To understand the inconsistency between the clinical cure and the presence of "residual disease" at a molecular level, we separated and identified the cells expressing AML1/ETO by phenotype and function. Here we demonstrate that AML1/ETO transcripts are present in a fraction of stem cells, monocytes, and B cells in remission marrow, and in a fraction of B cells in leukemic marrow, but not in T cells. AML1/ETO transcripts also were demonstrated in a fraction of colony-forming cells of erythroid, granulocyte-macrophage, and/or megakaryocyte lineages in both leukemic and remission marrow. These data strongly suggest that the acquisition of the t(8;21) occurs at the level of stem cells capable of differentiating into B cells as well as all myeloid lineages, and that a fraction of the AML1/ETO-expressing stem cells undergo additional oncogenic event(s) that ultimately leads to transformation into AML.
在大多数处于长期缓解期的t(8;21)急性髓性白血病（AML）患者中可检测到白血病特异性AML1/ETO转录本。为了在分子水平上理解临床治愈与“残留疾病”存在之间的不一致性，我们通过表型和功能分离并鉴定了表达AML1/ETO的细胞。在此我们证明，AML1/ETO转录本存在于缓解期骨髓中的一部分干细胞、单核细胞和B细胞中，以及白血病骨髓中的一部分B细胞中，但不存在于T细胞中。AML1/ETO转录本在白血病和缓解期骨髓中红系、粒-巨噬系和/或巨核系的一部分集落形成细胞中也得到证实。这些数据有力地表明，t(8;21)的获得发生在能够分化为B细胞以及所有髓系谱系的干细胞水平，并且一部分表达AML1/ETO的干细胞会经历额外的致癌事件，最终导致转化为AML。
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