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Endothelial progenitor cells are clonal and exhibit JAK2V617F mutation in a subset of thrombotic patients with Ph-negative myeloproliferative neoplasms.
MedLine Citation:
PMID:  21212285     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In this study we investigated whether neoplastic transformation occurring in Ph-negative Myeloproliferative Neoplasms (MPN) could involve also the endothelial cell compartment. We evaluated the level of endothelial colony forming cells (ECFC) in 42 patients (15 with polycythemia vera, 12 with essential thrombocythemia and 15 with primary myelofibrosis (PMF). All patients had one or more molecular abnormality (JAK2(V617F) or MPL(W515K) mutations, SOCS genes hypermethylation, clonal pattern of growth) detectable in their granulocytes. The growth of colonies was obtained in 22 patients and, among them, patients with PMF exhibited the highest level of ECFC. We found that ECFC exhibited no molecular abnormalities in 12 patients, had SOCS gene hypermethylation and were polyclonal at the HUMARA assay in 5 patients, and resulted JAK2(V617F) mutated and clonal pathway in 5 additional patients, all experiencing thrombotic complications. On the whole, patients with altered ECFC required antiproliferative therapy more frequently than patients with normal ECFC. Moreover JAK2(V617F) positive ECFC showed a STAT5 and STAT3 phosphorylation rate higher than ECFC isolated from healthy individuals and from MPN patients without molecular abnormalities. Finally, JAK2(V617F) positive ECFC exhibited a high proficiency to adhere to normal mononuclear cells. This study highlights a novel mechanism underlying the thrombophilia observed in MPN.
Authors:
Luciana Teofili; Maurizio Martini; Maria Grazia Iachininoto; Sara Capodimonti; Eugenia Rosa Nuzzolo; Lorenza Torti; Tonia Cenci; Luigi Maria Larocca; Giuseppe Leone
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-6
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Hematology and Pathology, Catholic University, Rome, Italy.
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