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Updated: Aug 14, 2026

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
Published on: April 22, 2019
Collagen Turnover Is Associated with Disease Severity, Bone Marrow Fibrosis, and the JAK2V617F Variant Allele
Caroline Norup Bistrup1,2, Morten Kranker Larsen3, Peter Junker4
1Nordic Bioscience A/S, 2730 Herlev, Denmark.
Abstract:
Background and objectives: Myeloproliferative neoplasms (MPNs) are blood cancers characterized by elevated blood cell counts, bone marrow fibrosis (BMF), and chronic inflammation, which drives disease progression. BMF results from disrupted collagen turnover in the bone marrow extracellular matrix (ECM), making its reduction or stabilization a key therapeutic goal. Non-invasive biomarkers reflecting collagen turnover could potentially improve early detection of BMF and monitor disease activity. Methods: We evaluated serum biomarkers of collagen turnover in 130 MPN patients (MPN subtypes: ET = 49, PV = 60, pre-PMF = 8, PMF = 13) included in the DALIAH trial (ClinicalTrials.gov identifier: #NCT01387763). Type I and type III collagen formation (PRO-C1 and PRO-C3) and MMP-degraded type I, III, and IV collagens (C1M, C3M, and C4M) were measured by ELISA in serum. Biomarker levels were compared to age- and sex-matched healthy individuals and were assessed according to disease subtypes, somatic driver mutations, JAK2V617F VAF, and fibrosis grade. Furthermore, we studied correlations between the biomarker levels and conventional hematological markers for disease activity, such as hemoglobin, white blood cell count (WBCs), platelet counts, and lactate dehydrogenase (LDH). Results: Baseline PRO-C3 (p = 0.0005) and C1M (p = 0.0102) were elevated in MPN patients compared to healthy individuals, whereas C3M was decreased (p < 0.0001). Patients with primary myelofibrosis (PMF) had higher levels of PRO-C3 compared to patients with ET (p = 0.0041) and PV (p = 0.0172), correlated with higher JAK2V617F VAF (≥50%) (p = 0.0069) and advanced fibrosis grade (p = 0.0002). In addition, PRO-C3 was positively correlated to LDH, which is a biomarker of disease activity in MPNs (r = 0.5754, p < 0.0001). Conclusions: Taken together, these findings emphasize the role of ECM remodeling in MPN pathophysiology and the potential of soluble ECM neoepitopes as biologically plausible disease markers.
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