Abstract
Though the diagnostic criteria of myeloid metaplasia with myelofibrosis (MMM) are now well established, the origin and pathophysiological mechanisms of this myeloproliferative disorder remain unclear. Concerning its pathophysiology, myeloproliferation and myelofibrosis are the intrinsic characteristics of the disease. Whereas the myeloproliferation was shown to result from a clonal amplification of primitive progenitor cells, fibroblast proliferation appeared to be polyclonal, thus suggesting that myelofibrosis was a reactive process. The myeloproliferation observed in MMM patients is characterized by an increased number of circulating CD34+ hematopoietic progenitors. When cultured at high concentration without added exogenous growth factors, unpurified progenitors from MMM patients gave rise to spontaneous colonies of all myeloid lineages. Such an autonomous growth disappeared when purified CD34+ progenitors were plated. These results suggested that growth factors are involved in the dysregulation of proliferation and/or differentiation of MMM hematopoietic progenitors. Cytokines such as PDGF, TGF-β, and bFGF, produced mainly by megakaryocytes, have been proposed to be involved in the abnormal activation of fibroblasts, resulting in fibrosis. Recently the role of the fibrogenic cytokines, TGF-β and bFGF, in the regulation of primitive hematopoiesis has been reported. The aim of this review is to address the question of the potential dual implication of TGF-β and bFGF in the pathogenesis of both myelofibrosis and myeloproliferation in MMM patients.
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Received: January 7, 1999 / Accepted: April 26, 1999
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Le Bousse-Kerdilès, M., Martyré, M. & Members of the French INSERM Research Network on Idiopathic Myelofibrosis. Dual implication of fibrogenic cytokines in the pathogenesis of fibrosis and myeloproliferation in myeloid metaplasia with myelofibrosis. Ann Hematol 78, 437–444 (1999). https://doi.org/10.1007/s002770050595
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DOI: https://doi.org/10.1007/s002770050595