Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy.
Neoplasia. 2012 Nov;14(11):1057-66. doi: 10.1593/neo.12736.
Cell fusion plays a well-recognized physiological role during development, while its function during progression is still unclear. Here, we show that acute myeloid leukemia (AML) cells spontaneously fused with murine host cells in vivo. AML cells fused in most cases with mouse macrophages. Other targets of AML cell fusion were dendritic and endothelial cells. Cytogenetic and molecular analysis revealed that successive recipients conserved detectable amounts of parental DNA. Moreover, in a mouse AML1-ETO model where female AML1-ETO-leukemic cells, expressing CD45.2, were injected in congenic CD45.1 male mice AML cells, we found hybrid cells expressing both allelic types of CD45 and XXY set of sexual chromosomes. More importantly, the fusion protein AML1-ETO was transferred in the hybrid cells. When sorted hybrid cells were reinjected in a secondary recipient, they gave rise to leukemia with 100% penetrance and similar time of onset of leukemic cells. Our data indicate that in vivo fusion of cancer cells with host cells may be a mechanism of gene transfer for cancer dissemination and suggest that fused cells may be used to identify still unrecognized leukemogenic genes that are conserved in hybrid cells and able to perpetuate leukemia in vivo.
细胞融合在发育过程中起着公认的生理作用，但其在进展过程中的功能尚不清楚。在这里，我们表明急性髓系白血病（AML）细胞在体内自发地与小鼠宿主细胞融合。AML 细胞在大多数情况下与小鼠巨噬细胞融合。AML 细胞融合的其他靶标是树突状细胞和内皮细胞。细胞遗传学和分子分析显示，连续的受者保留了可检测到的亲本 DNA 量。此外，在 AML1-ETO 模型中，我们将表达 CD45.2 的雌性 AML1-ETO-白血病细胞注射到同基因 CD45.1 雄性小鼠中，AML 细胞，我们发现表达两种 CD45 等位基因类型和 XXY 性染色体的杂交细胞。更重要的是，融合蛋白 AML1-ETO 转移到杂交细胞中。当对杂交细胞进行分选并再次注入二次受者时，它们会导致白血病，其白血病细胞的出现率为 100%，且发病时间相似。我们的数据表明，癌细胞与宿主细胞的体内融合可能是癌症传播的基因转移机制，并表明融合细胞可用于鉴定在杂交细胞中保守且能够在体内持续存在白血病的尚未识别的白血病基因。
