{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:30:00Z","timestamp":1787625000378,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Essential thrombocythemia (ET) is a myeloproliferative disorder characterized as excessive platelet production. Early and accurate diagnosis is critical to manage the disease and prevent progression to serious myeloid neoplasms like myelofibrosis or acute myeloid leukemia, though definitive diagnosis remains challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We retrieved seven publicly available microarray datasets from GEO database. Data preprocessing included normalization and batch correction using limma and SVA packages. Differentially expressed genes (DEGs) were identified via robust rank aggregation (RRA). Protein-protein interaction networks, GO and KEGG analyses were performed. qRT-PCR was used to verify the expression of key genes in control subjects and patients with ET. Immune infiltration was analyzed with CIBERSORT, while logistic regression and LASSO models validated the diagnostic potential of the identified genes. Functional assays including shRNA knockdown, CCK-8, apoptosis detection, and Western blot were conducted in primary CD34+ cell-derived megakaryocytes from ET patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven key DEGs were identified, and the logistic regression model achieved area under the curve of 0.846 and 0.863 for the training and test sets, respectively. Immune infiltration analysis revealed significant changes in B, T, and NK cells. The qRT-PCR analysis revealed\n                      <jats:italic>BP1<\/jats:italic>\n                      ,\n                      <jats:italic>MMP8<\/jats:italic>\n                      , and\n                      <jats:italic>CEACAM8<\/jats:italic>\n                      up-regulated in ET patients. In particular,\n                      <jats:italic>LCN2<\/jats:italic>\n                      and\n                      <jats:italic>MMP8<\/jats:italic>\n                      were functionally validated: knockdown of either gene significantly reduced cell viability and promoted apoptosis in megakaryocytes. Further analysis showed that MMP8 knockdown was associated with reduced IL-17 signaling, while LCN2 knockdown led to inhibition of the NOD-like receptor pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified an eleven-gene signature that links IL-17 and NOD-like receptor signaling to megakaryocyte dysfunction and immune dysregulation in ET.\n                      <jats:italic>In vitro<\/jats:italic>\n                      functional experiments suggested that LCN2 and MMP8 may contribute to megakaryocyte survival and inflammatory pathway activation. These findings provide a foundation for further investigation into the roles of LCN2 and MMP8 in ET pathogenesis and highlight them as candidates for future functional studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1741533","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:53:46Z","timestamp":1777442026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dysregulation of the immune microenvironment in essential thrombocythemia: the interplay of core genes and inflammation-related signaling pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Yeqiong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Hematology, People\u2019s Hospital of Ningxia Hui Autonomous Region","place":["Yinchuan, Ningxia Hui Autonomous Region, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huicheng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Third Clinical College of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Third Clinical College of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Third Clinical College of Ningxia Medical University","place":["Yinchuan, Ningxia Hui Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of 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