TGF-β1: Key role in myelofibrosis
Chagraoui H., Tulliez M., Vainchenker W., Wendling F.
Bone marrow fibrosis is the diagnostic criteria of agnogenic myeloid metaplasia, a chronic myeloproliferative disorder characterized by a prominent accumulation of extracellular matrix within the bone marrow environment. An array of cytokines or humoral growth factors secreted from the proliferative hematopoietic malignant clone has been hypothesized to be responsible for the increased collagen synthesis by bone marrow fibroblasts. Among these factors, TGF-β1, PDGF, bFGF and IL-1 released from megakaryocytes and monocytes are thought to play key roles in myelofibrosis promotion. However, their respective impact is still unclear. The creation of a murine model of myelofibrosis that mimics the evolution of agnogenic myeloid metaplasia and the use of TGF-β1 knock-out mice provide evidence that TGF-β1 released by hematopoietic cells is pivotal for the pathogenesis of myelofibrosis. This manuscript summarizes the main results obtained in vivo and raises some important questions to fully understand the mechanisms leading to myelofibrosis.