A robust xenotransplantation model for acute myeloid leukemia.
A robust xenotransplantation model for acute myeloid leukemia.
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人类急性髓性白血病（AML）在免疫功能低下动物中的异种移植对于定义白血病干细胞至关重要。然而，现有的免疫缺陷小鼠品系寿命短，AML细胞植入水平低，阻碍了对原代人AML生物学的长期评价。最近的一项研究表明，NOD/LtSz-scid IL 2 R γc null（NSG）小鼠增强了AML细胞植入，但这依赖于技术上具有挑战性的新生儿注射。在这里，我们使用尾静脉注射对成年NSG小鼠中的AML植入进行了广泛的分析。在分析的35个AML样本中，66%显示骨髓植入超过0.1%。此外，37%显示出高水平的植入（>10%），有些高达95%。AML细胞扩增2-44倍。二级和三级受体显示出一致的植入，大多数显示出进一步的AML细胞扩增。植入与法国-美国-英国亚型或细胞遗传学异常无关。然而，具有FLT 3突变的样品显示出比FLT 3野生型更高的植入概率。重要的是，动物发展出器官肿大和与晚期白血病一致的消耗性疾病。我们的结论是，NSG异种移植模型是一个强大的人AML细胞移植模型，这将允许更好地表征AML生物学和新疗法的测试。
Xenotransplantation of human acute myeloid leukemia (AML) in immunocompromised animals has been critical for defining leukemic stem cells. However, existing immunodeficient strains of mice have short life spans and low levels of AML cell engraftment, hindering long-term evaluation of primary human AML biology. A recent study suggested that NOD/LtSz-scid IL2Rγc null (NSG) mice have enhanced AML cell engraftment, but this relied on technically challenging neonatal injections. Here, we performed extensive analysis of AML engraftment in adult NSG mice using tail vein injection. Of the 35 AML samples analyzed, 66% showed bone marrow engraftment over 0.1%. Further, 37% showed high levels of engraftment (>10%), with some as high as 95%. A 2–44-fold expansion of AML cells was often seen. Secondary and tertiary recipients showed consistent engraftment, with most showing further AML cell expansion. Engraftment did not correlate with French–American–British subtype or cytogenetic abnormalities. However, samples with FLT3 mutations showed a higher probability of engraftment than FLT3 wild type. Importantly, animals developed organomegaly and a wasting illness consistent with advanced leukemia. We conclude that the NSG xenotransplantation model is a robust model for human AML cell engraftment, which will allow better characterization of AML biology and testing of new therapies.