Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia.
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.
Duke Scholars
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Related Subject Headings
- Transplantation Chimera
- Survival Rate
- RNA Interference
- Protein Serine-Threonine Kinases
- Oncology & Carcinogenesis
- Oncogenes
- Mice, Inbred C57BL
- Mice
- Leukemia, Myeloid, Acute
- Intracellular Signaling Peptides and Proteins
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transplantation Chimera
- Survival Rate
- RNA Interference
- Protein Serine-Threonine Kinases
- Oncology & Carcinogenesis
- Oncogenes
- Mice, Inbred C57BL
- Mice
- Leukemia, Myeloid, Acute
- Intracellular Signaling Peptides and Proteins