Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies
| Autor: | Ronald Hoffman, Abdallah Abou Zahr, Srdan Verstovsek, John Mascarenhas, Ruben A. Mesa, Douglas Tremblay, Nicole Carreau, Mohamed E. Salama |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty medicine.medical_treatment Bone Marrow Cells Hematopoietic stem cell transplantation Review Article Severity of Illness Index 03 medical and health sciences 0302 clinical medicine Megakaryocyte Fibrosis Bone Marrow medicine Animals Humans Genetic Predisposition to Disease Molecular Targeted Therapy Progenitor cell Myelofibrosis Tumor microenvironment business.industry Hematology medicine.disease Prognosis Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cell Transformation Neoplastic Cellular Microenvironment Primary Myelofibrosis 030220 oncology & carcinogenesis Disease Progression Bone marrow business |
| Zdroj: | Haematologica. 101(6) |
| ISSN: | 1592-8721 |
| Popis: | Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. |
| Databáze: | OpenAIRE |
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