Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction
Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction
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DOI：
10.1182/blood-2009-02-206565
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发表时间：
2010-03-11
期刊：
影响因子：
20.3
通讯作者：
Bonnet, Dominique
中科院分区：
文献类型：
--
作者：
Taussig, David C.;Vargaftig, Jacques;Bonnet, Dominique
急性髓性白血病（AML）中的白血病起始细胞（lic）被认为局限于CD34（+）部分。然而，AML中最常见的突变基因之一是核磷蛋白（NPM），这与CD34的低表达有关。因此，我们研究了npm突变的aml是否具有仅限于CD34（+）部分的lic。我们将原代npm突变AML的分选部分移植到免疫缺陷小鼠体内，以确定哪些部分引发白血病。大约一半的病例仅在CD34（-）部分中具有LICs，而CD34（-）部分包含正常的多系造血再填充细胞。其余大多数病例在CD34（-）和CD34（-）两部分均有lccs。当样本根据CD34和CD38的表达进行分类时，多个部分在原发性和继发性受体中引发白血病。数据表明，LICs的表型比以前认识到的更加异质性，甚至在单个样本中也可能发生变化。llic的这一特点可能使它们特别难以使用针对表面抗原的治疗来根除。（《Blood》，2010;115:1976-1984）
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. (Blood. 2010; 115: 1976-1984)