MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
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DOI：
10.1016/j.ccr.2004.10.015
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发表时间：
2004-12-01
期刊：
影响因子：
50.3
通讯作者：
Gilliland, DG
中科院分区：
文献类型：
--
作者：
Huntly, BJP;Shigematsu, H;Gilliland, DG
为了更好地了解白血病干细胞的起源，我们测试了所有白血病癌基因可以转化缺乏自我更新能力的定向髓系祖细胞的假设，正如最近报道的MLL-ENL。分别用癌基因MOZ-TIF 2和BCR-ABL转导普通髓系祖细胞和粒细胞-单核细胞祖细胞的流式分选群体。MOZ-TIF 2转导的祖细胞可以在甲基纤维素培养物中连续再接种，并在液体培养物中连续繁殖，并导致可以连续移植的体内急性髓性白血病。相反，BCR-ABL转导没有赋予造血祖细胞这些特性。这些数据表明，一些，但不是全部，白血病癌基因可以赋予白血病干细胞的属性，注定要经历凋亡细胞死亡的造血祖细胞。
To better understand the origin of leukemic stem cells, we tested the hypothesis that all leukemia oncogenes could transform committed myeloid progenitor cells lacking the capacity for self-renewal, as has recently been reported for MLL-ENL. Flow-sorted populations of common myeloid progenitors and granulocyte-monocyte progenitors were transduced with the oncogenes MOZ-TIF2 and BCR-ABL, respectively. MOZ-TIF2-transduced progenitors could be serially replated in methylcellulose cultures and continuously propagated in liquid culture, and resulted in an acute myeloid leukemia in vivo that could be serially transplanted. In contrast, BCR-ABL transduction conferred none of these properties to hematopoietic progenitors. These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death.