Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis
Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understand...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/415024 |
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| author | Christophe Desterke Christophe Martinaud Nadira Ruzehaji Marie-Caroline Le Bousse-Kerdilès |
| author_facet | Christophe Desterke Christophe Martinaud Nadira Ruzehaji Marie-Caroline Le Bousse-Kerdilès |
| author_sort | Christophe Desterke |
| collection | DOAJ |
| description | Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies. |
| format | Article |
| id | doaj-art-e13fefbf39e44dbd91dcab0ad005e9e7 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e13fefbf39e44dbd91dcab0ad005e9e72025-08-20T03:25:59ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/415024415024Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary MyelofibrosisChristophe Desterke0Christophe Martinaud1Nadira Ruzehaji2Marie-Caroline Le Bousse-Kerdilès3Inserm UMS33, Paul Brousse Hospital, 14 Avenue Paul-Vaillant Couturier, 94800 Villejuif, FranceDepartment of Clinical Biology, HIA Percy, 101 Avenue Henri Barbusse, 92140 Clamart, FranceInserm UMR-S1197, Paul Brousse Hospital, 14 Avenue Paul-Vaillant Couturier, 94800 Villejuif, FranceInserm UMR-S1197, Paul Brousse Hospital, 14 Avenue Paul-Vaillant Couturier, 94800 Villejuif, FrancePrimary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies.http://dx.doi.org/10.1155/2015/415024 |
| spellingShingle | Christophe Desterke Christophe Martinaud Nadira Ruzehaji Marie-Caroline Le Bousse-Kerdilès Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis Mediators of Inflammation |
| title | Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis |
| title_full | Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis |
| title_fullStr | Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis |
| title_full_unstemmed | Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis |
| title_short | Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis |
| title_sort | inflammation as a keystone of bone marrow stroma alterations in primary myelofibrosis |
| url | http://dx.doi.org/10.1155/2015/415024 |
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