{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:39:23Z","timestamp":1786444763081,"version":"build-2736575974"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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. Oncol."],"abstract":"<jats:p>\n                    The neutrophil-to-lymphocyte ratio (NLR) has emerged as a mechanistically informative biomarker in clonal hematopoiesis of indeterminate potential (CHIP) and myeloproliferative neoplasms (MPNs), although its clinical utility is strongly mutation dependent. NLR is markedly elevated in\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    -mutated CHIP and MPNs, reflecting neutrophil-driven myeloproliferation, whereas it remains largely unchanged in\n                    <jats:italic>TET2<\/jats:italic>\n                    ,\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    , and\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations despite substantial IL-1\u03b2- and IL-6-mediated inflammation. This apparent paradox highlights distinct inflammatory programs generated by different driver mutations, with JAK2 promoting neutrophilia and epigenetic mutations primarily activating macrophage-mediated innate immunity. In polycythemia vera, elevated NLR independently predicts thrombosis, myelofibrotic progression, and mortality. Similar prognostic value has been reported in essential thrombocythemia and myelofibrosis, particularly among patients with\n                    <jats:italic>JAK2<\/jats:italic>\n                    mutations. Beyond risk stratification, NLR also functions as a pharmacodynamic biomarker. During treatment with ropeginterferon alfa-2b, reductions in NLR parallel decreases in\n                    <jats:italic>JAK2V617F<\/jats:italic>\n                    allele burden, whereas persistent NLR elevation during hydroxyurea therapy identifies patients at higher risk of thrombosis and adverse outcomes. Conversely, the CANTOS trial demonstrates that patients with\n                    <jats:italic>TET2<\/jats:italic>\n                    -mutated CHIP derived marked cardiovascular benefit from IL-1\u03b2 inhibition despite NLR providing limited biological information, underscoring the need for complementary biomarkers in non-JAK2 CHIP. This review integrates mechanistic, clinical, and therapeutic evidence supporting mutation-specific inflammatory biomarkers and proposes NLR-guided strategies for risk assessment, treatment monitoring, and precision management in MPNs and CHIP.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1926319","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:23:50Z","timestamp":1786443830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil-to-lymphocyte ratio as a gene-specific biomarker of JAK2-driven inflammation across CHIP and myeloproliferative neoplasms"],"prefix":"10.3389","volume":"16","author":[{"given":"Tiziano","family":"Barbui","sequence":"first","affiliation":[{"name":"FROM - Research Foundation Bergamo Hospital - Ente del Terzo Settore (ETS)","place":["Bergamo, 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