Abstract
A feature that distinguishes chronic idiopathic myelofibrosis (CIM) from other chronic myeloproliferative disorders is the progression to bone marrow fibrosis and osteosclerosis. Because osteoclast formation can be inhibited by osteoprotegerin (OPG), we investigated its megakaryocytes’ expression and serum concentration in patients (pts) with CIM (n=20, median age 64 years, range 46–81) and in 20 controls showing no evidence of neoplastic disease (median age 62 years, range 46–82). The study group comprised 10 pts with prefibrotic cellular CIM and 10 with severe fibrosis. Assessment of OPG concentration in serum was performed using Osteoprotegerin ELISA Kit (Biomedica, Austria). EnVision (DAKO) kit with monoclonal anti-human osteoprotegerin/TNFRSF11B antibody - MAB8051 (R&D Systems, USA) was used to evaluate OPG expression in megakaryocytes. Gomori silver staining technique was applied for semi-quantitative assessment of bone marrow fibrosis according to increased amount of reticulin fibers. OPG serum levels in pts with CIM were significantly higher than in controls (105.78 vs 85.14 pg/ml, p=0.02), and showed positive correlation with age in both groups (r=0.61, p=0.0037 and r=0.55, p=0.012, respectively). Serum levels of OPG in pts with CIM patients were not associated with erythrocyte, leukocyte, platelet numbers and with the Visani, Lille or Cervantes prognostic scores. There was no correlation between serum levels of OPG and its expression in megakaryocytes in pts and controls. In megakaryocytes derived from patients with CIM as well as from controls, OPG expression was detected, but in those derived from CIM hematopoiesis (at any stage of the disease) were significantly higher. OPG expression in megakaryocytes derived from prefibrotic CIM was significantly lower than from advanced stages of the disease (p=0.007).
We conclude that OPG appears to be involved in bone marrow fibrosis in CIM through overexpression by megakariocyte.
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