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Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with
Abstract:
Platelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c-sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patients.
Insights
Platelet-derived growth factor (PDGF) mRNA is elevated in myeloproliferative disorder (MPD) patients, suggesting a role in myelofibrosis pathogenesis. This may involve increased PDGF synthesis in megakaryocytes, contributing to bone marrow fibrosis.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Myelofibrosis is a serious complication of myeloproliferative disorders (MPDs).
- Platelet-derived growth factor (PDGF) is implicated in the pathogenesis of myelofibrosis.
- The specific role of PDGF in MPD-associated myelofibrosis requires further elucidation.
Purpose of the Study:
- To investigate the expression levels of PDGF mRNA in bone marrow megakaryocytes of MPD patients.
- To explore the correlation between PDGF A and B chain mRNA expression.
- To assess the potential contribution of PDGF to myelofibrosis in MPDs.
Main Methods:
- In situ hybridization was used to quantify PDGF A and B chain mRNA in bone marrow megakaryocytes from 13 MPD patients and controls.
- cDNA probes for human PDGF A and B chains (c-sis) were utilized.
- Marrow fibroblast proliferation assays were performed on purified megakaryocytes.
Main Results:
- PDGF A and B chain mRNA levels were significantly higher in MPD patients compared to controls.
- Elevated mRNA levels were particularly noted in patients with essential thrombocythemia and polycythemia vera.
- PDGF activity in megakaryocytes showed no significant difference between MPD patients and controls, despite high mRNA levels.
Conclusions:
- Increased PDGF mRNA expression in megakaryocytes of MPD patients suggests a potential role in myelofibrosis.
- A possible mechanism involves high PDGF synthesis in megakaryocytes with subsequent release into the bone marrow environment.
- These findings highlight PDGF as a potential therapeutic target in MPD-related myelofibrosis.