{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:41:16Z","timestamp":1777862476066,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by the activation of the JAK\u2010STAT pathway. Previous evidence showed that metformin might be a possible therapeutic option for treating JAK2\u2010mediated myeloproliferative neoplasms. In vitro and in vivo studies demonstrated that metformin inhibits the JAK\u2010STAT pathway, induces apoptosis in JAK2\n                    <jats:sup>V617F<\/jats:sup>\n                    \u2010positive cell lines and reduces tumor burden and splenomegaly in Jak2\n                    <jats:sup>V617F<\/jats:sup>\n                    knock\u2010in\u2010induced mice. The FIBROMET trial, an open label phase II study, evaluated metformin effects on 10 primary myelofibrosis patients over 2\u00a0years of treatment. Primary endpoint was bone marrow fibrosis reduction. Secondary endpoints were constitutional symptoms, blood counts, spleen size modulation and exploratory evaluation of protein and gene expression. Metformin treatment reduced bone marrow collagen deposits, downregulated the STAT pathway and reduced the p85 subunit of PI3K enzymatic complex, together with endothelial maintenance genes, in PMF patients. These results raise new evidence regarding metformin, a cheap and widely available drug, as a possible adjuvant for the treatment of PMF patients.\n                  <\/jats:p>","DOI":"10.1002\/hon.70163","type":"journal-article","created":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T14:01:23Z","timestamp":1766930483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Downregulates the STAT Pathway and Reduces Bone Marrow Fibrosis in Primary Myelofibrosis Patients: Final Results of the Phase II FIBROMET Trial"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-7203","authenticated-orcid":false,"given":"Paula de","family":"Melo Campos","sequence":"first","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1tia Borgia Barbosa","family":"Pagnano","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Soares","family":"Niemann","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rubia Isler","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Isabel","family":"Della Via","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7347-6534","authenticated-orcid":false,"given":"Ada","family":"Congrains","sequence":"additional","affiliation":[{"name":"Hematology and Transfusion Medicine Center Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Luiz","family":"Coelho\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Hematology and Oncology Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c2ngela Condotta","family":"Tinoco","sequence":"additional","affiliation":[{"name":"Department of Pathology Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilherme Rossi","family":"Assis\u2010Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Pathology Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Luiz Lopes de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Pathology Universidade Estadual de Campinas (Unicamp)  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Traina","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Hematology and Oncology Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-3667","authenticated-orcid":false,"given":"Sara T. 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