Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia.
Journal Article (Journal Article)
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 retrovirally 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/EBPalpha. 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/EBPalpha.
Full Text
Duke Authors
Cited Authors
- Keeshan, K; He, Y; Wouters, BJ; Shestova, O; Xu, L; Sai, H; Rodriguez, CG; Maillard, I; Tobias, JW; Valk, P; Carroll, M; Aster, JC; Delwel, R; Pear, WS
Published Date
- November 2006
Published In
Volume / Issue
- 10 / 5
Start / End Page
- 401 - 411
PubMed ID
- 17097562
Pubmed Central ID
- PMC2839500
International Standard Serial Number (ISSN)
- 1535-6108
Digital Object Identifier (DOI)
- 10.1016/j.ccr.2006.09.012
Language
- eng
Conference Location
- United States