Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, Queen Mary University of London, London.
Blood. 2010 Mar 11;115(10):1976-84. doi: 10.1182/blood-2009-02-206565. Epub 2010 Jan 6.
Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34(+) fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34(+) fraction. We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately one-half of cases had LICs exclusively within the CD34(-) fraction, whereas the CD34(+) fraction contained normal multilineage hematopoietic repopulating cells. Most of the remaining cases had LICs in both CD34(+) and CD34(-) fractions. When samples were sorted based on CD34 and CD38 expression, multiple fractions initiated leukemia in primary and secondary recipients. The data indicate that the phenotype of LICs is more heterogeneous than previously realized and can vary even within a single sample. This feature of LICs may make them particularly difficult to eradicate using therapies targeted against surface antigens.
急性髓系白血病 (AML) 中的白血病起始细胞 (LICs) 被认为仅限于 CD34(+) 部分。然而，AML 中最常突变的基因之一是核磷蛋白 (NPM)，这与 CD34 表达水平低有关。因此，我们研究了 NPM 突变的 AML 是否具有仅限于 CD34(+) 部分的 LICs。我们将原代 NPM 突变 AML 的分选部分移植到免疫缺陷小鼠中，以确定哪些部分引发白血病。大约一半的病例的 LICs 仅存在于 CD34(-) 部分，而 CD34(+) 部分含有正常的多谱系造血重建造血细胞。其余大多数病例的 LICs 存在于 CD34(+) 和 CD34(-) 部分。当根据 CD34 和 CD38 表达对样本进行分选时，多个部分在原发性和继发性受者中引发了白血病。数据表明，LICs 的表型比以前认识到的更加异质，甚至在单个样本中也可能发生变化。LICs 的这种特征可能使它们特别难以用针对表面抗原的疗法根除。
