期刊
PLOS BIOLOGY
卷 8, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1000476
关键词
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资金
- INSERM
- La Ligue Nationale contre le Cancer
- Fondation Salus Sanguinis
- Action de Recherche Concertee (ARC) of the Universite catholique de Louvain [MEXP31C1]
- Fondation contre le cancer
- Atlantic Philanthropies, New York
- PAI Program, Belgium [BCHM61B5]
- Fonds National de la Recherche Scientifique (FNRS), Belgium
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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