Malignant transformation initiated by MII-AF9: Gene dosage and critical target cells
Malignant transformation initiated by MII-AF9: Gene dosage and critical target cells
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DOI：
10.1016/j.ccr.2008.03.005
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发表时间：
2008-05-01
期刊：
影响因子：
50.3
通讯作者：
Kersey, John H.
中科院分区：
文献类型：
--
作者：
Chen, Weili;Kumar, Ashish R.;Kersey, John H.
致癌基因，如MLL-AF9，在人类和小鼠中启动转化和白血病的途径尚未完全确定。在靶细胞和癌基因剂量的研究中，我们发现在内源性调控下，MII-AF9能有效转化LSK (Lin(-)Scal（+)c-kit(+)）干细胞，而承诺的粒细胞-单核细胞祖细胞（GMPs）具有转化抗性，不会引起白血病。MII-AF9在造血干细胞（HSC）中的表达水平高于GMP细胞。MII-AF9基因的剂量效应直接体现在实验中，通过逆转录病毒转导导致的高剂量MII-AF9有效转化gmp。MII-AF9上调了192个基因在LSK和祖细胞中的表达，但在LSK中的表达水平高于在骨髓祖细胞中的表达水平。
The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that MII-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin(-)Scal(+)c-kit(+)) stem cells, while committed granulocyte-monocyte progenitors (GMPs) were transformation resistant and did not cause leukemia. MII-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. MII-AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of MII-AF9 resulting from retroviral transduction. MII-AF9 upregulated expression of 192 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.