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Systemic transforming growth factor-beta in patients with bone marrow fibrosis--pathophysiological implications
P Rameshwar1, V T Chang, U F Thacker
1Department of Medicine-Hematology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
American Journal of Hematology
|October 10, 1998
Summary
Transforming growth factor beta (TGF-beta) is significantly elevated in patients with bone marrow fibrosis, irrespective of its cause. This finding suggests TGF-beta plays a key role in myelofibrosis development and offers a potential biomarker for early intervention.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Myelofibrosis, including idiopathic myelofibrosis (IMF) and secondary myelofibrosis (MF), is characterized by bone marrow fibrosis, neoangiogenesis, and increased extracellular matrix (ECM) proteins.
- These pathological features are potentially linked to transforming growth factor beta (TGF-beta), a cytokine primarily produced by monocytes.
- Elevated and activated monocytes with increased intracytoplasmic TGF-beta are observed in myelofibrosis.
Purpose of the Study:
- To determine systemic levels of TGF-beta in patients with bone marrow (BM) fibrosis compared to those without.
- To investigate the specific isoform and activity of TGF-beta in patients with BM fibrosis.
- To assess the potential role of basic fibroblast growth factor (bFGF) in BM fibrosis.
Main Methods:
- Systemic TGF-beta levels were measured in sera from patients with IMF (n=18), MF (n=16), hematologic disorders without fibrosis (n=40), and normal controls (n=27).
- In situ hybridization and immunohistochemical analyses were performed on BM biopsy sections to localize TGF-beta1.
- Serum levels of basic fibroblast growth factor (bFGF) were quantified.
Main Results:
- A significant elevation of TGF-beta was observed in the sera of patients with BM fibrosis compared to those without (P < 0.0001).
- Over 80% of the elevated TGF-beta was active and belonged to the beta1 isoform, predominantly detected in myelomonocytic areas within the BM of fibrotic patients.
- TGF-beta elevation was detected in 100% of fibrotic patients, whereas bFGF elevation was found in only 57%.
Conclusions:
- Systemic TGF-beta is consistently elevated in patients with bone marrow fibrosis, regardless of the underlying etiology.
- TGF-beta, particularly the TGF-beta1 isoform, is strongly implicated in the pathogenesis of bone marrow fibrosis.
- Elevated TGF-beta levels represent a significant potential biomarker for early therapeutic intervention in myelofibrosis.