In Vitro Megakaryocyte Differentiation and Proplatelet Formation in Ph-Negative Classical Myeloproliferative Neoplasms: Distinct Patterns in the Different Clinical Phenotypes
| Autor: | Marco Cattaneo, Vittorio Rosti, Denis V. Baev, Stefania Badalucco, Annalisa De Silvestri, Alessandra Balduini, Maria Teresa Pugliano, Giovanni Barosi |
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| Rok vydání: | 2011 |
| Předmět: |
Platelets
Blood Platelets Anatomy and Physiology Lineage (genetic) Science Megakaryocyte differentiation Immunology Bone Marrow Cells In Vitro Techniques Immunophenotyping Hematologic Cancers and Related Disorders Myeloproliferative Disorders Polycythemia vera Megakaryocyte Bone Marrow Immune Physiology hemic and lymphatic diseases Molecular Cell Biology BIO/11 Biologia molecolare Humans Medicine Philadelphia Chromosome Myelofibrosis Biology Multidisciplinary business.industry Essential thrombocythemia Cancers and Neoplasms Cell Differentiation Hematology medicine.disease Hematopoiesis medicine.anatomical_structure Oncology Immune System Case-Control Studies Mutation Clinical Immunology Cellular Types business Megakaryocytes Research Article |
| Zdroj: | PLoS ONE, Vol 6, Iss 6, p e21015 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0021015 |
| Popis: | Background: Ph-negative myeloproliferative neoplasms (MPNs) are clonal disorders that include primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET). Although the pathogenesis of MPNs is still incompletely understood, an involvement of the megakaryocyte lineage is a distinctive feature. Methodology/Principal Findings: We analyzed the in vitro megakaryocyte differentiation and proplatelet formation in 30 PMF, 8 ET, 8 PV patients, and 17 healthy controls (CTRL). Megakaryocytes were differentiated from peripheral blood CD34+ or CD45+ cells in the presence of thrombopoietin. Megakaryocyte output was higher in MPN patients than in CTRL with no correlation with the JAK2 V617F mutation. PMF-derived megakaryocytes displayed nuclei with a bulbous appearance, were smaller than ET- or PV-derived megakaryocytes and formed proplatelets that presented several structural alterations. In contrast, ET- and PV-derived megakaryocytes produced more proplatelets with a striking increase in bifurcations and tips compared to both control and PMF. Proplatelets formation was correlated with platelet counts in patient peripheral blood. Patients with pre-fibrotic PMF had a pattern of megakaryocyte proliferation and proplatelet formation that was similar to that of fibrotic PMF and different from that of ET. Conclusions/Significance: In conclusion, MPNs are associated with high megakaryocyte proliferative potential. Profound differences in megakaryocyte morphology and proplatelet formation distinguish PMF, both fibrotic and prefibrotic, from ET and PV. |
| Databáze: | OpenAIRE |
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