title: Involvement of the fibrogenic cytokines, TGF-beta and bFGF, in the pathogenesis of idiopathic myelofibrosis.
abstract: Idiopathic Myelofibrosis (IMF), is a chronic myeloproliferative disorder characterized by the association of myeloproliferation and myelofibrosis. The pathophysiological mechanisms resulting in this disease remain still unclear. The myeloproliferation appeared to result from the clonal amplification of hematopoietic progenitors. In contrast, fibroblasts participating in myelofibrosis were shown to be polyclonal, thus suggesting that myelofibrosis was a reactive process. We studied the role of two growth factors TGF-beta and bFGF, which display potent fibrogenic properties and are major regulators of primitive hematopoiesis, in IMF pathogenesis. We demonstrated an increase of TGF-beta and bFGF expression in circulating megakaryocytic cells and platelets, together with alterations of the expression of these cytokines and their receptors in hematopoietic CD34+ progenitor cells from IMF patients. Our results suggested that TGF-beta and bFGF are involved both in myelofibrosis and myeloproliferation which characterize IMF.
authors.affiliation: INSERM U268, IFR André Lwoff, hôpital Paul Brousse, 14, avenue Paul-Vaillant Couturier, 94800, Villejuif, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Le Bousse-Kerdilès
authors.forename: M C
authors.initials: MC
authors.lastname: Martyré
mesh_terms: D019898:Autocrine Communication; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005347:Fibroblasts / Q000473:pathology; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism; D008954:Models, Biological; D055728:Primary Myelofibrosis / Q000209:etiology* / Q000503:physiopathology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016298:Hematopoietic Cell Growth Factors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2