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| Status |
Public on Jan 29, 2013 |
| Title |
Oncostatin M effects in IMR90 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| Overall design |
IMR90 cells were treated with a single dose of rh Oncostatin M (10ng/ml).
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| |
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| Contributor(s) |
Hörmann G, Bilban M, Mayerhofer M |
| Citation(s) |
22051730 |
| |
| Submission date |
Jun 01, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Martin Bilban |
| E-mail(s) |
Martin.Bilban@meduniwien.ac.at
|
| Phone |
++43 (0)1 40400 6441
|
| Organization name |
Medical University of Vienna
|
| Department |
|
| Street address |
|
| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA141247 |
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