Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia
Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia
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DOI：
10.1016/j.ccr.2006.09.012
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发表时间：
2006-11-01
期刊：
影响因子：
50.3
通讯作者：
Pear, Warren S.
中科院分区：
文献类型：
--
作者：
Keeshan, Karen;He, Yiping;Pear, Warren S.
tribles同源物2 （Trib2）在生长停滞的白血病细胞中被鉴定为下调转录物。为了研究Trib2在造血祖细胞中的作用，我们用逆转录病毒表达Trib2的造血干细胞重组小鼠。trib2转导的骨髓细胞在体外表现出生长优势，并且易于建立因子依赖性细胞系。在体内，重组trib2的小鼠均发生致死性可移植急性髓性白血病（AML）。在机制研究中，我们发现Trib2与C/EBP α相关并抑制其表达。此外，Trib2在人类AML患者样本的一部分中表达升高。总之，我们的数据确定Trib2是一种致癌基因，通过涉及C/EBP α失活的机制诱导AML。
Tribbles homolog 2 (Trib2) was identified as a downregulated transcript in leukemic cells undergoing growth arrest. To investigate the effects of Trib2 in hematopoietic progenitors, mice were reconstituted with hematopoietic stem cells retro-virally expressing Trib2. Trib2-transduced bone marrow cells exhibited a growth advantage ex vivo and readily established factor-dependent cell lines. In vivo, Trib2-reconstituted mice uniformly developed fatal transplantable acute myelogenous leukemia (AML). In mechanistic studies, we found that Trib2 associated with and inhibited C/EBP alpha. Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBP alpha.