TRANSFORMING GROWTH-FACTOR-BETA AND MEGAKARYOCYTES IN THE PATHOGENESIS OF IDIOPATHIC MYELOFIBROSIS

Although the disease is well described, the pathogenesis of bone marro w fibrosis in idiopathic myelofibrosis still remains unclear. We previ ously reported elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in patients with this myeloproliferative disorder, c ompared with healthy subjects. Here, in a series of 16 patients, we sh ow that TGF-beta expression is also increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Nort hern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as evalua ted in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells. By immunostaining with a polyclonal a nti-TGF-beta(1) antibody, TGF-P was localized in morphologically heter ogenous cells: these cells were characterized as megakaryocytes by lab elling with a gpII(b)III(a) monoclonal antibody. Thus we provide evide nce that both TGF-beta and megakaryocytes are linked in the pathogenes is of idiopathic myelofibrosis.