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

来源：

CANCER CELL | 2008年 / 13卷 / 05期

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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