Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-β in patients with myelofibrosis with myeloid metaplasia

Authors


Dr Marie-Claire Martyré, Unité 196 INSERM, Institut Curie, Section de Biologie, 26 rue d'Ulm, 75005 Paris, France.

Abstract

Summary. Platelet-derived growth factor (PDGF) is thought to play some role in the genesis of fibrosis associated with myeloproliferative disorders. In addition, transforming growth factor-β (TGF-β) has been confirmed to promote fibrotic process. Both PDGF and TGF-β have been shown to cooperate with epidermal growth factor (EGF) in regulating the growth of human marrow fibroblasts. All three are contained in platelet α-granules.

We report the results of a study in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF, TGF-β and EGF-like activities in circulating platelets from patients compared to healthy subjects. In contrast to EGF-like intraplatelet levels which were similar in patients and in normal donors (1-4 ng/109 platelets), we found constantly higher values for both PDGF and TGF-β in MMM patients. In both radioimmunoassay (RIA) and assay for mitogenic activity on human bone marrow fibroblasts, PDGF levels were increased on the average 2-3·5-fold over the levels found in normal donors (P<0·01 and P<0·001, respectively). PDGF serum levels in patients were consistent with those found in platelets. In platelet-poor plasma (PPP), PDGF concentrations were undetectable or ≃ 2 ng/ml in patients and in control donors as well. The total TGF-β activity in platelet lysates, determined using a competitive radioreceptor binding assay on Swiss 3T3 mouse cells and an inhibition growth assay on CCL64 cells, was found 2-3-fold increased in patients with MMM as compared to control subjects (P<0·003).

These results emphasize that, not only PDGF, but also TGF-β are implicated in the myelofibrosis with myeloid metaplasia.

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