Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis.
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-beta (TGF-beta) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-beta expression is also increased in patients' peripheral 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-beta 1 antibody, TGF-beta 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-beta and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.
Martyré
M C
MC
Unité 365 INSERM, Institut Curie, Section de Biologie, Paris, France.
Romquin
N
N
Le Bousse-Kerdiles
M C
MC
Chevillard
S
S
Benyahia
B
B
Dupriez
B
B
Demory
J L
JL
Bauters
F
F
D000368:Aged; D001483:Base Sequence; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D055728:Primary Myelofibrosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D016212:Transforming Growth Factor beta