| Anti-inflammatory cytokines hepatocyte growth factor and interleukin-11 are over-expressed in Polycythemia vera and contribute to the growth of clonal erythroblasts independently of JAK2V617F. | |
| | |
MedLine Citation:
|
PMID: 21042281 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
The V617F activating mutation of janus kinase 2 (JAK2), a kinase essential for cytokine signalling, characterizes Polycythemia vera (PV), one of the myeloproliferative neoplasms (MPN). However, not all MPNs carry mutations of JAK2, and in JAK2-mutated patients, expression of JAK2V617F does not always result in clone expansion. In the present study, we provide evidence that inflammation-linked cytokines are required for the growth of JAK2V617F-mutated erythroid progenitors. In a first series of experiments, we searched for cytokines over-expressed in PV using cytokine antibody (Ab) arrays, and enzyme-linked immunosorbent assays for analyses of serum and bone marrow (BM) plasma, and quantitative reverse transcription-PCRs for analyses of cells purified from PV patients and controls. We found that PV patients over-expressed anti-inflammatory hepatocyte growth factor (HGF) and interleukin-11 (IL-11), BM mesenchymal stromal cells (BMMSCs) and erythroblasts being the main producers. In a second series of experiments, autocrine/paracrine cytokine stimulation of erythroblasts was blocked using neutralizing Abs specific for IL-11 or c-MET, the HGF receptor. The growth of JAK2V617F-mutated HEL cells and PV erythroblasts was inhibited, indicating that JAK2-mutated cells depend on HGF and IL-11 for their growth. Additional experiments showed that transient expression of JAK2V617F in BaF-3/erythropoietin receptor cells, and invalidation of JAK2V617F in HEL cells using anti-JAK2 small interfering RNA, did not affect HGF and IL-11 expression. Thus, anti-inflammatory HGF and IL-11 are upregulated in PV and their overproduction is not a consequence of JAK2V617F. As both cytokines contribute to the proliferation of PV erythroblasts, blocking the c-MET/HGF/IL-11 pathways could be of interest as an additional therapeutic option in PV. |
| | |
Authors:
|
M Boissinot; C Cleyrat; M Vilaine; Y Jacques; I Corre; S Hermouet |
Publication Detail:
|
Type: Journal Article Date: 2010-11-01 |
Journal Detail:
|
Title: Oncogene Volume: 30 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-02-24 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
|
Languages: eng Pagination: 990-1001 Citation Subset: IM |
Affiliation:
|
INSERM UMR 892, Institut de Biologie, Centre Hospitalier Universitaire, Nantes, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patien...
Next Document: Disruption of NAD(P)H:quinone oxidoreductase 1 gene in mice leads to 20S proteasomal degradation of ...