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Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia.

ABSTRACT: 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.

SUBMITTER: Keeshan K

PROVIDER: S-EPMC2839500 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia.

Keeshan Karen K He Yiping Y Wouters Bas J BJ Shestova Olga O Xu Lanwei L Sai Hong H Rodriguez Carlos G CG Maillard Ivan I Tobias John W JW Valk Peter P Carroll Martin M Aster Jon C JC Delwel Ruud R Pear Warren S WS

Cancer cell 20061101 5

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). ...[more]

PMID: 17097562

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NF1 inactivation in adult acute myelogenous leukemia

2010-12-02 | GSE21107 | GEO

NF1 inactivation in adult acute myelogenous leukemia

Project description:Purpose: This study was conducted to identify novel genes with importance to the biology of adult acute myelogenous leukemia (AML). Conclusions: NF1 null states are present in 7/95=7% of adult AML and delineate a disease subset that could be preferentially targeted by Ras or mTOR-directed therapeutics. Experimental design: We analyzed DNA from highly purified AML blasts and paired buccal cells from 95 patients for recurrent genomic microdeletions using ultra-high density Affymetrix SNP 6.0 array-based genomic profiling. 006, 096 and 136 normal Samples have been excluded from study.

2010-12-02 | E-GEOD-21107 | biostudies-arrayexpress

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