Linked Life Data

21042281

Source:http://linkedlifedata.com/resource/pubmed/id/21042281

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-2-24
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
990-1001
pubmed:meshHeading
pubmed-meshheading:21042281-Cell Proliferation, pubmed-meshheading:21042281-Clone Cells, pubmed-meshheading:21042281-Cytokines, pubmed-meshheading:21042281-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21042281-Erythroblasts, pubmed-meshheading:21042281-Female, pubmed-meshheading:21042281-Gene Expression Profiling, pubmed-meshheading:21042281-Hepatocyte Growth Factor, pubmed-meshheading:21042281-Humans, pubmed-meshheading:21042281-Inflammation, pubmed-meshheading:21042281-Interleukin-11, pubmed-meshheading:21042281-Janus Kinase 2, pubmed-meshheading:21042281-Male, pubmed-meshheading:21042281-Mutation, pubmed-meshheading:21042281-Polycythemia Vera, pubmed-meshheading:21042281-RNA, Messenger, pubmed-meshheading:21042281-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21042281-Signal Transduction, pubmed-meshheading:21042281-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
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.
pubmed:affiliation
INSERM UMR 892, Institut de Biologie, Centre Hospitalier Universitaire, Nantes, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't