{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:51Z","timestamp":1790315991769,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neutrophils are increasingly recognized as dynamic regulators of tumor inflammation and immune remodeling. Neutrophil extracellular trap (NET)-related biomarkers have been implicated in cancer progression, but their clinical and immunological interpretation remains challenging because different circulating NET components may not represent equivalent biological processes. In multiple myeloma, a malignancy shaped by complex interactions among clonal plasma cells, hematopoiesis, and the bone marrow immune microenvironment, the relevance of distinct circulating NET-related markers remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured serum citrullinated histone H3 (Cit-H3) and myeloperoxidase-DNA complexes (MPO-DNA) in 171 patients with multiple myeloma and 15 healthy controls. Patients were categorized by disease status at sampling as newly diagnosed multiple myeloma, remission, or relapsed\/refractory multiple myeloma. Associations with disease status, inflammatory parameters, tumor burden, hematologic indices, R-ISS and R2-ISS stage, high-risk cytogenetic abnormalities, and exploratory survival outcomes were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum Cit-H3 levels were significantly higher in patients with multiple myeloma than in healthy controls and were highest in relapsed\/refractory disease. Cit-H3 was associated with lower lymphocyte counts and higher neutrophil-to-lymphocyte ratios. In contrast, serum MPO-DNA complexes were not significantly increased in the overall myeloma cohort compared with controls and were lower in relapsed\/refractory disease than in newly diagnosed or remission states. In exploratory correlation analyses, higher MPO-DNA levels were associated with higher hemoglobin and albumin levels, lower bone marrow plasma cell burden, and lower \u03b22-microglobulin. Cit-H3 and MPO-DNA levels were not significantly correlated, and neither marker was significantly associated with R-ISS or R2-ISS stage, del(17p), t(4;14), or 1q21 amplification. Exploratory survival analyses showed no statistically significant associations with progression-free or overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Circulating Cit-H3 and MPO-DNA complexes are not interchangeable NET-related biomarkers in multiple myeloma and do not simply reflect conventional clinical or cytogenetic risk stratification. Rather than representing a uniform NET signal, these markers may capture distinct aspects of neutrophil-related immune dysregulation, systemic inflammation, and hematopoietic status, highlighting the need for prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1960912","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:41Z","timestamp":1790314301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Cit-H3 and MPO-DNA complexes reveal divergent neutrophil-associated immune profiles in multiple myeloma"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingdi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiubai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","article-title":"Multiple myeloma","volume":"10","author":"Malard","year":"2024","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and management of multiple 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