Author/Authors :
Keeshan، نويسنده , , Karen and He، نويسنده , , Yiping and Wouters، نويسنده , , Bas J. and Shestova، نويسنده , , Olga and Xu، نويسنده , , Lanwei and Sai، نويسنده , , Hong and Rodriguez، نويسنده , , Carlos G. and Maillard، نويسنده , , Ivan and Tobias، نويسنده , , John W. and Valk، نويسنده , , Peter and Carroll، نويسنده , , Martin and Aster، نويسنده , , Jon C. and Delwel، نويسنده , , Ruud and Pear، نويسنده , , Warren S.، نويسنده ,
Abstract :
Summary
es 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/EBPα. 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/EBPα.
