Malignant transformation initiated by MII-AF9: Gene dosage and critical target cells

被引:166
作者
Chen, Weili [4 ]
Kumar, Ashish R. [1 ,4 ]
Hudson, Wendy A. [4 ]
Li, Quanzhi [4 ]
Wu, Baolin [3 ]
Staggs, Rodney A. [4 ]
Lund, Erik A. [4 ]
Sam, Thien N. [4 ]
Kersey, John H. [1 ,2 ,4 ]
机构
[1] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA
关键词
CELLCYCLE;
D O I
10.1016/j.ccr.2008.03.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:432 / 440
页数:9
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