Transforming growth factor-β and megakaryocytes in the pathogenesis of idiopathic myelofibrosis

Authors


Dr M. C. Martyré, Unité 365, INSERM, Section de Biologie, Institut Curie, 26 rue d'Ulm, 75231 Paris Cedex 05, France

Abstract

Summary. Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor-β (TGF-β) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-β expression is also increased in patients' periperal blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR): (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells.

By immunostaining with a polyclonal anti-TGF-β1 antibody, TGF-β was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody.

Thus we provide evidence that both TGF-β and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.

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