Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia.
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-beta (TGF-beta) has been confirmed to promote fibrotic process. Both PDGF and TGF-beta have been shown to cooperate with epidermal growth factor (EGF) in regulating the growth of human marrow fibroblasts. All three are contained in platelet alpha-granules. We report the results of a study in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF, TGF-beta 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/10(9) platelets), we found constantly higher values for both PDGF and TGF-beta 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 less than 0.01 and P less than 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 congruent to 2 ng/ml in patients and in control donors as well. The total TGF-beta 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 less than 0.003). These results emphasize that, not only PDGF, but also TGF-beta are implicated in the myelofibrosis with myeloid metaplasia.
Martyré
M C
MC
Unité 196 INSERM, Institut Curie, Paris, France.
Magdelenat
H
H
Bryckaert
M C
MC
Laine-Bidron
C
C
Calvo
F
F
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D055728:Primary Myelofibrosis / Q000097:blood* / Q000150:complications / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000097:blood*
D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor