{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T04:44:35Z","timestamp":1786164275065,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 &lt; 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 (\u226550%) (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 &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers18152529","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:52:30Z","timestamp":1786031550000},"page":"2529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Collagen Turnover Is Associated with Disease Severity, Bone Marrow Fibrosis, and the JAK2V617F Variant Allele Frequency in Myeloproliferative Neoplasms"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8009-6033","authenticated-orcid":false,"given":"Caroline Norup","family":"Bistrup","sequence":"first","affiliation":[{"name":"Nordic Bioscience A\/S, 2730 Herlev, Denmark"},{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Kranker","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-9964","authenticated-orcid":false,"given":"Peter","family":"Junker","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-7826","authenticated-orcid":false,"given":"Vibe","family":"Skov","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Kj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-3099","authenticated-orcid":false,"given":"Trine Alma","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5026-8740","authenticated-orcid":false,"given":"Morten","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience A\/S, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Willumsen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience A\/S, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-8032","authenticated-orcid":false,"given":"Hans Carl","family":"Hasselbalch","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1056\/NEJMra1406186","article-title":"Myeloproliferative Neoplasms","volume":"376","author":"Spivak","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/sj.leu.2404955","article-title":"Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms","volume":"22","author":"Tefferi","year":"2008","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1182\/blood.2022017416","article-title":"Biology and therapeutic targeting of molecular mechanisms in MPNs","volume":"141","author":"How","year":"2023","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1182\/blood.2022017578","article-title":"Genetic basis and molecular profiling in myeloproliferative neoplasms","volume":"141","author":"Kralovics","year":"2023","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1182\/blood-2016-10-695940","article-title":"Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms","volume":"129","author":"Vainchenker","year":"2017","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/bcj.2016.75","article-title":"Molecular characterisation of triple negative essential thrombocythaemia patients by platelet analysis and targeted sequencing","volume":"6","author":"Angona","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1182\/blood.2022017625","article-title":"Essential thrombocythemia: Challenges in clinical practice and future prospects","volume":"141","author":"Godfrey","year":"2023","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1182\/blood-2011-11-394775","article-title":"Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: Is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?","volume":"119","author":"Hasselbalch","year":"2012","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11899-019-00508-w","article-title":"Key Role of Inflammation in Myeloproliferative Neoplasms: Instigator of Disease Initiation, Progression. and Symptoms","volume":"14","author":"Blackmon","year":"2019","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.leukres.2012.10.020","article-title":"Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?","volume":"37","author":"Hasselbalch","year":"2013","journal-title":"Leuk. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"660","DOI":"10.3324\/haematol.2015.141283","article-title":"Bone marrow fibrosis in myelofibrosis: Pathogenesis, prognosis and targeted strategies","volume":"101","author":"Zahr","year":"2016","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.addr.2017.07.014","article-title":"The good and the bad collagens of fibrosis\u2014Their role in signaling and organ function","volume":"121","author":"Karsdal","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ajh.2830330105","article-title":"Procollagen type III aminoterminal peptide in serum in idiopathic myelofibrosis and allied conditions: Relation to disease activity and effect of chemotherapy","volume":"33","author":"Hasselbalch","year":"1990","journal-title":"Am. J. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/ajh.2830230204","article-title":"Serum markers for type IV collagen and type III procollagen in the myelofibrosis-osteomyelosclerosis syndrome and other chronic myeloproliferative disorders","volume":"23","author":"Hasselbalch","year":"1986","journal-title":"Am. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/BF00598910","article-title":"The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis","volume":"8","author":"Vellenga","year":"1983","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3109\/1354750X.2011.557440","article-title":"Post-translational modifications of the extracellular matrix are key events in cancer progression: Opportunities for biochemical marker development","volume":"16","author":"Leeming","year":"2011","journal-title":"Biomarkers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2217\/fon.12.161","article-title":"Bringing Cancer Serological Diagnosis to a New Level: Focusing on HER2, Protein Ectodomain Shedding and Neoepitope Technology","volume":"9","author":"Wang","year":"2013","journal-title":"Future Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hasselbalch, H.C., Junker, P., Skov, V., Kj\u00e6r, L., Knudsen, T.A., Larsen, M.K., Holmstr\u00f6m, M.O., Andersen, M.H., Jensen, C., and Karsdal, M.A. (2023). Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms. Cancers, 15.","DOI":"10.3390\/cancers15174323"},{"key":"ref_21","first-page":"303","article-title":"The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters","volume":"5","author":"Nielsen","year":"2013","journal-title":"Am. J. Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1755-1536-3-5","article-title":"Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats","volume":"3","author":"Veidal","year":"2010","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.clinbiochem.2010.07.025","article-title":"Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)\u2014Assessment of corresponding epitopes","volume":"43","author":"Leeming","year":"2010","journal-title":"Clin. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.clinbiochem.2010.03.012","article-title":"A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen","volume":"43","author":"Barascuk","year":"2010","journal-title":"Clin. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3109\/1354750X.2011.620628","article-title":"A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)","volume":"16","author":"Leeming","year":"2011","journal-title":"Biomarkers"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sand, J.M., Larsen, L., Hogaboam, C., Martinez, F., Han, M.L., Larsen, M.R., Nawrocki, A., Zheng, Q., Karsdal, M.A., and Leeming, D.J. (2013). MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis\u2014Validation of two novel biomarker assays. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084934"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1182\/blood-2007-04-083501","article-title":"Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: Recommendations from an ad hoc international expert panel","volume":"110","author":"Tefferi","year":"2007","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1182\/bloodadvances.2021004856","article-title":"Genomic profiling of a randomized trial of interferon-a vs hydroxyurea in MPN reveals mutation-specific responses","volume":"6","author":"Knudsen","year":"2022","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/j.1365-2141.2007.06497.x","article-title":"The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders","volume":"136","author":"Larsen","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000101708","article-title":"Myelofibrosis\u2014What\u2019s in a name? Consensus on definition and EUMNET grading","volume":"74","author":"Thiele","year":"2007","journal-title":"Pathobiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1034\/j.1600-0609.2003.00134.x","article-title":"Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders: Correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism","volume":"71","author":"Jensen","year":"2003","journal-title":"Eur. J. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1600-0609.1985.tb02827.x","article-title":"Serum procollagen III peptide in chronic myeloproliferative disorders","volume":"35","author":"Hasselbalch","year":"1985","journal-title":"Scand. J. Haematol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bella, J., and Hulmes, D.J.S. (2017). Fibrillar collagens. Fibrous Proteins: Structures and Mechanisms, Springer.","DOI":"10.1007\/978-3-319-49674-0_14"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41408-017-0024-9","article-title":"Marked elevation of serum lactate dehydrogenase in primary myelofibrosis: Clinical and prognostic correlates","volume":"7","author":"Shah","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5710","DOI":"10.1182\/blood-2010-07-293761","article-title":"Essential thrombocythemia versus early primary myelofibrosis: A multicenter study to validate the WHO classification","volume":"117","author":"Thiele","year":"2011","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1182\/blood-2007-05-091850","article-title":"Bone marrow pathology in essential thrombocythemia: Interobserver reliability and utility for identifying disease subtypes","volume":"111","author":"Wilkins","year":"2008","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1309\/AJCP2UG9SGGWAHUA","article-title":"Reproducibility of Histologic Classification in Nonfibrotic Myeloproliferative Neoplasia","volume":"136","author":"Koopmans","year":"2011","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1365-2559.2010.03545.x","article-title":"Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis","volume":"56","author":"Brousseau","year":"2010","journal-title":"Histopathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/apm.12417","article-title":"WHO classification 2008 of myeloproliferative neoplasms: A workshop learning effect\u2014The Danish experience","volume":"123","author":"Madelung","year":"2015","journal-title":"APMIS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/ajh.23554","article-title":"World Health Organization-defined classification of myeloproliferative neoplasms: Morphological reproducibility and clinical correlations\u2014The Danish experience","volume":"88","author":"Madelung","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.exphem.2009.07.005","article-title":"JAK2 V617F allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis","volume":"37","author":"Hussein","year":"2009","journal-title":"Exp. Hematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1371\/journal.pone.0015277","article-title":"High Frequency of Endothelial Colony Forming Cells Marks a Non-Active Myeloproliferative Neoplasm with High Risk of Splanchnic Vein Thrombosis","volume":"5","author":"Rosti","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Balduini, A., Badalucco, S., Pugliano, M.T., Baev, D., De, A., Cattaneo, M., Rosti, V., and Barosi, G. (2011). In Vitro Megakaryocyte Differentiation and Proplatelet Formation in Ph-Negative Classical Myeloproliferative Neoplasms: Distinct Patterns in the Different Clinical Phenotypes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021015"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1600-0463.2011.02754.x","article-title":"The JAK2V617F allele burden and STAT3- and STAT5 phosphorylation in myeloproliferative neoplasms: Early prefibrotic myelofibrosis compared with essential thrombocythemia, polycythemia vera and myelofibrosis","volume":"119","author":"Risum","year":"2011","journal-title":"APMIS"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Barosi, G., Rosti, V., Bonetti, E., Campanelli, R., Carolei, A., Catarsi, P., Isgr\u00f2, A.M., Lupo, L., Massa, M., and Poletto, V. (2012). Evidence that Prefibrotic Myelofibrosis Is Aligned along a Clinical and Biological Continuum Featuring Primary Myelofibrosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035631"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100051","DOI":"10.1016\/j.bvth.2025.100051","article-title":"Cardiovascular risk factors in myeloproliferative neoplasms: Associations with survival and thrombotic outcomes","volume":"2","author":"How","year":"2025","journal-title":"Blood Vessels Thromb. Hemost."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5825","DOI":"10.1182\/bloodadvances.2023010588","article-title":"JAK2V617F mutation is highly prevalent in patients with ischemic stroke: A case-control study","volume":"7","author":"Kristiansen","year":"2023","journal-title":"Blood Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1182\/blood-2005-09-3826","article-title":"Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders","volume":"107","author":"Passamonti","year":"2006","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/leu.2010.148","article-title":"A prospective study of 338 patients with polycythemia vera: The impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications","volume":"24","author":"Passamonti","year":"2010","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1182\/bloodadvances.2022007128","article-title":"Hematopoietic fitness of JAK2V617F myeloproliferative neoplasms is linked to clinical outcome","volume":"6","author":"Choi","year":"2022","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E645","DOI":"10.1097\/HS9.0000000000000645","article-title":"New Perspectives of Interferon-alpha2 and Inflammation in Treating Philadelphia-negative Chronic Myeloproliferative Neoplasms","volume":"5","author":"Hasselbalch","year":"2021","journal-title":"Hemasphere"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1182\/bloodadvances.2025018011","article-title":"Towards New Therapy Endpoints in Polycythemia Vera: Targeting Clonal and Towards New Therapy Endpoints in Polycythemia Vera: Targeting Clonal and Inflammatory Pathways Running title: New Therapy Endpoints in Polycythemia Vera","volume":"10","author":"Barbui","year":"2025","journal-title":"Blood Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100757","DOI":"10.1016\/j.diff.2024.100757","article-title":"Type 1 collagen: Synthesis, structure and key functions in bone mineralization","volume":"136","author":"Selvaraj","year":"2024","journal-title":"Differentiation"},{"key":"ref_54","first-page":"1128","article-title":"European consensus on grading bone marrow fibrosis and assessment of cellularity","volume":"90","author":"Thiele","year":"2005","journal-title":"Haematologica"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1365-2141.2007.06807.x","article-title":"Bone marrow fibrosis: Pathophysiology and clinical significance of increased bone marrow stromal fibres","volume":"139","author":"Kuter","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1242\/dmm.004077","article-title":"Remodeling and homeostasis of the extracellular matrix: Implications for fibrotic diseases and cancer","volume":"4","author":"Cox","year":"2011","journal-title":"Dis. Models Mech."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1080\/00365513.2021.2001045","article-title":"Reference interval for type III procollagen (PIIINP) using the Advia centaur PIIINP assay in adults and elderly","volume":"81","author":"Samyn","year":"2021","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/00365513.2021.1929444","article-title":"Procollagen III, N-terminal propeptide (PIIINP): Establishment of reference intervals in Northern European adults and children using the MAGLUMI 800 chemiluminescence immunoassay","volume":"81","author":"Larsen","year":"2021","journal-title":"Scand. J. Clin. Lab. Investig."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T04:30:40Z","timestamp":1786163440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":59,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152529"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152529","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}