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/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.

doi.org/10.1016/j.ccr.2006.09.012, hdl.handle.net/1765/67160
Cancer Cell
Department of Hematology

Keeshan, K, He, Y, Wouters, B.J, Shestova, O, Xu, L, Sai, H, … Pear, W.S. (2006). Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia. Cancer Cell, 10(5), 401–411. doi:10.1016/j.ccr.2006.09.012