Transcriptomics

Dataset Information

4

Oncostatin M effects in IMR90 cells


ABSTRACT: The JAK2 mutation V617F is detectable in a majority of patients with Ph-negative myeloproliferative neoplasms (MPN). Enforced expression of JAK2 V617F in mice induces myeloproliferation and bone marrow (BM) fibrosis suggesting a causal role for the JAK2 mutant in the pathogenesis of MPN. However, little is known about mechanisms and effector molecules contributing to JAK2 V617F-induced myeloproliferation and fibrosis. Here we show that JAK2 V617F promotes expression of oncostatin M (OSM) in neoplastic myeloid cells. Correspondingly, OSM was found to be overexpressed in the BM and elevated in the serum of patients with JAK2 V617F+ MPN. In addition, OSM secreted by JAK2 V617F+ cells stimulated growth of fibroblasts and microvascular endothelial cells and induced the production of angiogenic and profibrogenic cytokines (HGF, VEGF, and SDF-1) in BM fibroblasts. All effects of MPN cell-derived OSM were blocked by a neutralizing anti-OSM antibody, whereas the production of OSM in MPN cells was effectively suppressed by a pharmacologic JAK2 inhibitor or RNAi-mediated knockdown of JAK2. In summary, JAK2 V617F-mediated upregulation of OSM may contribute to fibrosis, neoangiogenesis, and the cytokine storm observed in JAK2 V617F+ MPN, suggesting that OSM could serve as a novel therapeutic target molecule in these neoplasms. IMR90 cells were treated with a single dose of rh Oncostatin M (10ng/ml).

ORGANISM(S): Homo sapiens  

SUBMITTER: Martin Bilban   Gregor Hörmann  Matthias Mayerhofer 

PROVIDER: E-GEOD-29655 | ArrayExpress | 2013-01-29

SECONDARY ACCESSION(S): GSE29655PRJNA141247

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2014-03-12 | E-GEOD-55798 | ArrayExpress
2014-03-12 | E-GEOD-55801 | ArrayExpress
2018-12-01 | E-MTAB-5028 | ArrayExpress
| GSE79534 | GEO
2015-02-20 | E-MTAB-3340 | ArrayExpress
| GSE120595 | GEO
| GSE103238 | GEO
| GSE103237 | GEO
2016-05-26 | PXD002782 | Pride
2014-06-03 | E-GEOD-54645 | ArrayExpress