{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:50:40Z","timestamp":1785919840970,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ankara University Scientific Research Projects Coordination Unit","award":["TCD 2023 2813"],"award-info":[{"award-number":["TCD 2023 2813"]}]},{"award":["TCD 2023 2813"],"award-info":[{"award-number":["TCD 2023 2813"]}],"id":[{"id":"https:\/\/ror.org\/01wntqw50","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Post-treatment erythrocytosis (PT-E+)\u2014an increase in red blood cell counts after therapy\u2014is an uncommon but reproducible finding in a subset of Hodgkin lymphoma (HL) survivors, and its biological basis remains undefined. Methods: A targeted DNA sequencing panel of 33 genes was used at diagnosis and during follow-up in PT-E+ patients and HL controls who did not develop erythrocytosis (E\u2212; those without increased red blood cells). Germline (inherited) and somatic (acquired) genetic variants were compared, and changes in variant frequency over time were assessed. Results: PT-E+ patients had a unique molecular profile. They showed inherited variants in genes that regulate oxygen sensing and red blood cell production (EPAS1, EGLN3, HIF3A, PKLR, SH2B3, and RAB4B-EGLN2). Rare, acquired mutations affecting hypoxia, HIF, and EPO pathways (EGLN1\/2\/3, EPAS1, HIF1A\/3A, VHL, EPO, and PKLR) were also found. These changes did not appear in E\u2212 controls, who instead had common clonal hematopoiesis mutations (DNMT3A, TET2, ASXL1, and JAK3). Most somatic variants in the hypoxia pathway in PT-E+ patients decreased or disappeared after treatment, which suggests these changes are temporary and influenced by the surrounding environment. Conclusions: PT-E+ is biologically different from polycythemia vera and from idiopathic or JAK2-unmutated erythrocytosis. Both inherited risk and HL-related hypoxic or inflammatory stress are present. This supports a two-hit model, in which genetically primed red blood cell pathways respond strongly to disease-related triggers. These results suggest a new way to understand erythrocytosis after HL treatment.<\/jats:p>","DOI":"10.3390\/cancers18152504","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:14:46Z","timestamp":1785917686000},"page":"2504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-Treatment Persistent Erythrocytosis in Patients with Hodgkin Lymphoma: Molecular Mechanisms Underlying the Pathogenesis of Erythrocytosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Derya","family":"Koyun","sequence":"first","affiliation":[{"name":"Hematology Department, Ankara University School of Medicine, Ankara 06620, Turkey"},{"name":"Hematology Department, Bitlis Eren University School of Medicine, Bitlis 13000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seher","family":"Y\u00fcksel","sequence":"additional","affiliation":[{"name":"Pathology Department, Ankara University School of Medicine, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinem","family":"Civriz Bozda\u011f","sequence":"additional","affiliation":[{"name":"Hematology Department, Ankara University School of Medicine, Ankara 06620, Turkey"},{"name":"Hematology Department, Ko\u00e7 University School of Medicine, Istanbul 34010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur","family":"Tuncal\u0131","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Ankara University School of Medicine, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u015f\u0131nsu","family":"Kuzu","sequence":"additional","affiliation":[{"name":"Pathology Department, Ankara University School of Medicine, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhit","family":"\u00d6zcan","sequence":"additional","affiliation":[{"name":"Hematology Department, Ankara University School of Medicine, Ankara 06620, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and histiocytic\/dendritic neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1038\/s41375-021-01290-6","article-title":"JAK2 unmutated erythrocytosis: Current diagnostic approach and therapeutic views","volume":"35","author":"Gangat","year":"2021","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/ajh.26920","article-title":"JAK2 unmutated erythrocytosis: 2023 update on diagnosis and management","volume":"98","author":"Gangat","year":"2023","journal-title":"Am. 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