{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:03:31Z","timestamp":1790701411199,"version":"4.1.0"},"reference-count":34,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research","award":["22K16315"],"award-info":[{"award-number":["22K16315"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: The mechanism underlying myelofibrosis, which is associated with poor prognosis in myelodysplastic syndromes (MDS), remains unclear. Methods: We investigated the mechanisms underlying myelofibrosis using peripheral blood mononuclear cells (PBMCs) from healthy donors, MDS92 cell culture supernatants and PolgA\/+ and PolgA\/A mice treated with high-dose romiplostim as an MDS model. We used the LEGENDplex\u2122 immunoassay to analyze cytokine levels in MDS92 culture supernatants and serum samples from 12 patients with MDS or acute myeloid leukemia with myelodysplasia-related cytogenetic abnormalities. Results: The MDS92 cell culture supernatants inhibited monocyte differentiation into fibrocytes and contained significantly lower levels of CXCL1 (C-X-C motif chemokine ligand 1), IL-6 (Interleukin-6), and CCL22 (C-C motif chemokine ligand 22) than PBMC culture supernatants from healthy donors. Among serum samples from patients with MDS, IL-18 level was positively correlated with myelofibrosis grade and splenomegaly. In PolgA\/A mice, the F4\/80high CD11blow\/int cell fraction of the spleen was significantly increased following romiplostim administration, compared with PolgA\/+ mice; however, worsening of splenomegaly was not observed. Furthermore, reticulin fibers were observed mainly in the subcortical region in all PolgA\/+ mice but were rare in the PolgA\/A mice. Conclusions: These findings suggest an association between altered cytokine signaling fibrocyte differentiation, and myelofibrosis in MDS. Further studies are required to clarify how cytokine levels and cellular responsiveness contribute to fibrocyte-mediated myelofibrosis.<\/jats:p>","DOI":"10.31083\/fbl54751","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:21:51Z","timestamp":1790698911000},"source":"Crossref","is-referenced-by-count":0,"title":["Elucidating Mechanisms Underlying Fibrocyte-Mediated Myelofibrosis Induction in Myelodysplastic Syndromes"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-0862","authenticated-orcid":true,"given":"Takaaki","family":"Maekawa","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"},{"name":"Division of Palliative Care, National Defense Medical College Hospital, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Mukai","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurika","family":"Yanaki","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kemmoku","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Shonai","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Sone","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Takada","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Ogata","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"},{"name":"Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 173-8610, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Tachi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikuni","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Osawa","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Defense Medical College, 359-8513 Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal 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