| A senescence-like cell-cycle arrest occurs during megakaryocytic maturation: implications for physiological and pathological megakaryocytic proliferation. | |
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MedLine Citation:
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PMID: 20838657 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombopoietin (TPO) via signaling through its cognate receptor MPL is a key cytokine involved in the regulation of megakaryocyte differentiation leading to platelet production. Mature megakaryocytes are polyploid cells that have arrested DNA replication and cellular proliferation but continue sustained protein synthesis. Here, we show that TPO induces cell-cycle arrest in the megakaryocytic UT7-MPL cell line by the activation of the ERK/MAPK pathway, induction of p21CIP transcription, and senescence markers through EGR1 activation. A similar senescence-like process was also detected in normal primary postmitotic megakaryocytes. In contrast, senescence was not observed in malignant megakaryocytes derived from primary myelofibrosis patients (a form of chronic myeloid hemopathy). Our data indicate that polyploid mature megakaryocytes receive signals from TPO to arrest cell proliferation and enter a senescent-like state. An escape from this physiological process may be associated with certain myeloproliferative neoplasms leading to abnormal megakaryocytic proliferation. |
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Authors:
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Rodolphe Besancenot; Ronan Chaligné; Carole Tonetti; Florence Pasquier; Caroline Marty; Yann Lécluse; William Vainchenker; Stefan N Constantinescu; Stéphane Giraudier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-07 |
Journal Detail:
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Title: PLoS biology Volume: 8 ISSN: 1545-7885 ISO Abbreviation: PLoS Biol. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-09-14 Completed Date: 2011-01-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101183755 Medline TA: PLoS Biol Country: United States |
Other Details:
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Languages: eng Pagination: - Citation Subset: IM |
Affiliation:
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INSERM, U790, Institut Gustave Roussy, Villejuif, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging* Cell Cycle* Cell Line Cell Proliferation* Humans Megakaryocytes / cytology*, drug effects Thrombopoietin / pharmacology |
| Chemical | |
Reg. No./Substance:
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9014-42-0/Thrombopoietin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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