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The possible role of mutated endothelial cells in myeloproliferative neoplasms
Myeloproliferative neoplasms (MPN) are chronic, clonal hematologic malignancies characterized by myeloproliferation and a high incidence of vascular complications (thrombotic and bleeding). Although MPN-specific driver mutations have been identified, the underlying events that culminate in these cli...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Fondazione Ferrata Storti
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561279/ https://www.ncbi.nlm.nih.gov/pubmed/34320782 http://dx.doi.org/10.3324/haematol.2021.278499 |
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author | Farina, Mirko Russo, Domenico Hoffman, Ronald |
author_facet | Farina, Mirko Russo, Domenico Hoffman, Ronald |
author_sort | Farina, Mirko |
collection | PubMed |
description | Myeloproliferative neoplasms (MPN) are chronic, clonal hematologic malignancies characterized by myeloproliferation and a high incidence of vascular complications (thrombotic and bleeding). Although MPN-specific driver mutations have been identified, the underlying events that culminate in these clinical manifestations require further clarification. We reviewed the numerous studies performed during the last decade identifying endothelial cell (EC) dysregulation as a factor contributing to MPN disease development. The JAK2V617F MPN mutation and other myeloid-associated mutations have been detected not only in hematopoietic cells but also in EC and their precursors in MPN patients, suggesting a link between mutated EC and the high incidence of vascular events. To date, however, the role of EC in MPN continues to be questioned by some investigators. In order to further clarify the role of EC in MPN, we first describe the experimental strategies used to study EC biology and then analyze the available evidence generated using these assays which implicate mutated EC in MPN-associated abnormalities. Mutated EC have been reported to possess a pro-adhesive phenotype as a result of increased endothelial Pselectin exposure, secondary to degranulation of Weibel-Palade bodies, which is further accentuated by exposure to pro-inflammatory cytokines. Additional evidence indicates that MPN myeloproliferation requires JAK2V617F expression by both hematopoietic stem cells and EC. Furthermore, the reports of JAK2V617F and other myeloid malignancy- associated mutations in both hematopoietic cells and EC in MPN patients support the hypothesis that MPN driver mutations may first appear in a common precursor cell for both EC and hematopoietic cells. |
format | Online Article Text |
id | pubmed-8561279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-85612792021-11-10 The possible role of mutated endothelial cells in myeloproliferative neoplasms Farina, Mirko Russo, Domenico Hoffman, Ronald Haematologica Review Article Myeloproliferative neoplasms (MPN) are chronic, clonal hematologic malignancies characterized by myeloproliferation and a high incidence of vascular complications (thrombotic and bleeding). Although MPN-specific driver mutations have been identified, the underlying events that culminate in these clinical manifestations require further clarification. We reviewed the numerous studies performed during the last decade identifying endothelial cell (EC) dysregulation as a factor contributing to MPN disease development. The JAK2V617F MPN mutation and other myeloid-associated mutations have been detected not only in hematopoietic cells but also in EC and their precursors in MPN patients, suggesting a link between mutated EC and the high incidence of vascular events. To date, however, the role of EC in MPN continues to be questioned by some investigators. In order to further clarify the role of EC in MPN, we first describe the experimental strategies used to study EC biology and then analyze the available evidence generated using these assays which implicate mutated EC in MPN-associated abnormalities. Mutated EC have been reported to possess a pro-adhesive phenotype as a result of increased endothelial Pselectin exposure, secondary to degranulation of Weibel-Palade bodies, which is further accentuated by exposure to pro-inflammatory cytokines. Additional evidence indicates that MPN myeloproliferation requires JAK2V617F expression by both hematopoietic stem cells and EC. Furthermore, the reports of JAK2V617F and other myeloid malignancy- associated mutations in both hematopoietic cells and EC in MPN patients support the hypothesis that MPN driver mutations may first appear in a common precursor cell for both EC and hematopoietic cells. Fondazione Ferrata Storti 2021-07-19 /pmc/articles/PMC8561279/ /pubmed/34320782 http://dx.doi.org/10.3324/haematol.2021.278499 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Review Article Farina, Mirko Russo, Domenico Hoffman, Ronald The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title | The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title_full | The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title_fullStr | The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title_full_unstemmed | The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title_short | The possible role of mutated endothelial cells in myeloproliferative neoplasms |
title_sort | possible role of mutated endothelial cells in myeloproliferative neoplasms |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561279/ https://www.ncbi.nlm.nih.gov/pubmed/34320782 http://dx.doi.org/10.3324/haematol.2021.278499 |
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