Platelet-derived growth factor concentrations in platelet-poor plasma and urine from patients with myeloproliferative disorders

Abstract

Our enzyme-linked immunosorbent assay (ELISA) for measuring human platelet-derived growth factor (PDGF) detects nanogram quantities (ranging from 0.007 to 16 ng/100 microL) in purified PDGF standards. This assay is sensitive enough for studying plasma and urine. The range in normal volunteers was 0.6 to 2.3 micrograms/L for platelet-poor plasma and 1.4 to 3.3 micrograms/L for urine. We determined PDGF levels in the circulation (outside platelets) in patients with myeloproliferative diseases. Platelet-poor plasma and urine PDGF were significantly elevated in patients with myelofibrosis (6.2 +/- 2.0 micrograms/L for plasma; 7.8 +/- 2.4 micrograms/L for urine) and essential thrombocythemia (5.5 +/- 1.5 micrograms/L for plasma; 11.4 +/- 2.2 micrograms/L for urine), but not in patients with chronic myelogenous leukemia (2.1 +/- 0.4 micrograms/L for plasma; 2.8 +/- 1.2 micrograms/L for urine). Polycythemia vera produced an intermediate pattern: although plasma PDGF was within the normal range (2.1 +/- 0.2 micrograms/L), urine levels were increased (3.7 +/- 0.6 micrograms/L). These results show that PDGF is increased in the circulation in some but not all myeloproliferative diseases, and suggest that this is due to abnormal in vivo release from either megakaryocytes in the bone marrow or circulating platelets.

Investigation of calmodulin and basic fibroblast growth factor (bFGF) in idiopathic myelofibrosis: evidence for a role of extracellular calmodulin in fibroblast proliferation

“…Since platelets are a rich source of releasable calmodulin Eastham et al, 1994), we suggest that this finding may reflect an abnormal secretion, or leakage, of calmodulin from defective megakaryocytes and/or platelets. Such an observation is in agreement with the elevated urinary levels reported for other platelet constituents in idiopathic myelofibrosis, namely PDGF (Gersuk et al, 1989) and platelet factor 4 (Burstein et al, 1984). No significant correlation was noted, however, between calmodulin excretion rates and clinical parameters in the patient population.…”

“…Groopman (1980) first proposed that the increased bone marrow stroma results from an inappropriate intramedullary release of platelet derived growth factor(s) (PDGF) from clonal megakaryocytes and/or platelets. In support of this hypothesis, a reduction in both platelet PDGF mitogenic and antigenic levels (Bernabie et al, 1986;Katoh et al, 1988;Dolan et al, 1991), as well as an increase in plasma and urinary PDGF have been reported in myelofibrotic patients (Gersuk et al, 1989). PDGF release, however, although undoubtedly inducing fibroblast growth, cannot account totally for the complexity of myelofibrotic stroma.…”

Variation of PDGF, TGFβ, and bFGF levels in essential thrombocythemia patients treated with anagrelide

“…Castro-Malaspina et al [3] have shown the role of platelet-derived growth factor (PDGF) released by megakaryocytes in the pathogenesis of MMM. Increased PDGF levels in platelet-poor plasma [4], in serum [5,6], and in platelet lysates [6,7] have been reported in these patients. In addition to PDGF, other growth factors, such as transforming growth factor beta (TGFb) and basic ®broblast growth factor (bFGF), were found involved in myelo®brosis.…”

The production of tissue inhibitors of metalloproteinases (TIMPs) in megakaryopoiesis: possible role of platelet‐ and megakaryocyte‐derived TIMPs in bone marrow fibrosis

“…The megakaryocytic lineage is believed to be pathogenetically important in the production of myelofibrotic stromal tissue (Reilly, 1994). Platelet-poor plasma and urine levels of PDGF are higher in patients with ET or MF than in normal controls (Gersuk et al, 1989). In addition to PDGF, TGF-b, platelet factor 4 and calmodulin secreted from megakaryocytes and platelets may contribute to the production of myelofibrotic stromal tissue (Reilly, 1993;Burstein et al, 1984;Eastham et al, 1994).…”