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The mechanism by which BM fibrosis develops and the factors that drive stromal activation and fibrosis are not well understood. Cellular Communication Network 2 (CCN2), also known as CTGF (Connective Tissue Growth Factor), is a profibrotic matricellular protein functioning as an important driver and biomarker of fibrosis in a wide range of diseases outside the marrow. CCN2 can promote fibrosis directly or by acting as a factor downstream of TGF-\u03b2, the latter already known to contribute to myelofibrosis in MPN.<\/jats:p><jats:p>To study the possible involvement of CCN2 in BM fibrosis in MPN, we assessed CCN2 protein expression by immunohistochemistry in 75 BM biopsies (55\u2009\u00d7\u2009MPN and 20\u2009\u00d7\u2009normal controls). We found variable expression of CCN2 in megakaryocytes with significant overexpression in a subgroup of 7 (13%) MPN cases; 4 of them (3\u2009\u00d7\u2009essential thrombocytemia and 1\u2009\u00d7\u2009prefibrotic primary myelofibrosis) showed no fibrosis (MF-0), 2 (1\u2009\u00d7\u2009post-polycythemic myelofibrosis and 1\u2009\u00d7\u2009primary myelofibrosis) showed moderate fibrosis (MF-2), and 1 (primary myelofibrosis) severe fibrosis (MF-3). Remarkably, CCN2 expression did not correlate with fibrosis or other disease parameters such as platelet count or thrombovascular events, neither in this subgroup nor in the whole study group. This suggests that in BM of MPN patients other, CCN2-independent pathways (such as noncanonical TGF-\u03b2 signaling) may be more important for the development of fibrosis.<\/jats:p>","DOI":"10.1007\/s00428-024-03799-4","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T13:01:57Z","timestamp":1712840517000},"page":"837-845","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CCN2\/CTGF expression does not correlate with fibrosis in myeloproliferative neoplasms, consistent with noncanonical TGF-\u03b2 signaling driving myelofibrosis"],"prefix":"10.1007","volume":"484","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-2802","authenticated-orcid":false,"given":"Roos J.","family":"Leguit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-9327","authenticated-orcid":false,"given":"Roel","family":"Broekhuizen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-2994","authenticated-orcid":false,"given":"Moniek","family":"de Witte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-4598","authenticated-orcid":false,"given":"Reinier A. 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