 |
Journal articles
A senescence-like cell-cycle arrest occurs during megakaryocytic maturation: implications for physiological and pathological megakaryocytic proliferation.
Abstract : 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.
Cited literature [43 references]
https://www.hal.inserm.fr/inserm-00707240
Contributor : Delphine Autard Connect in order to contact the contributor
Submitted on : Tuesday, June 12, 2012 - 11:49:44 AM
Last modification on : Thursday, October 21, 2021 - 5:10:59 AM
Long-term archiving on: : Thursday, September 13, 2012 - 2:25:31 AM
Contributor : Delphine Autard Connect in order to contact the contributor
Submitted on : Tuesday, June 12, 2012 - 11:49:44 AM
Last modification on : Thursday, October 21, 2021 - 5:10:59 AM
Long-term archiving on: : Thursday, September 13, 2012 - 2:25:31 AM
File
journal.pbio.1000476.pdf
Publisher files allowed on an open archive