{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:53:25Z","timestamp":1791604405190,"version":"4.3.4"},"reference-count":10,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune surveillance is increasingly recognized as a determinant of clonal selection in Philadelphia chromosome\u2010negative myeloproliferative neoplasms (MPN). While HLA\u2010restricted adaptive immune effects have been described, the contribution of inherited variation in natural killer (NK)\u2010cell regulatory pathways remains less well defined. We investigated whether killer immunoglobulin\u2010like receptor (KIR) allelic polymorphisms and HLA\u2013KIR receptor\u2013ligand interactions are associated with susceptibility to MPN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed high\u2010resolution next\u2010generation sequencing\u2010based KIR genotyping in 167 Bulgarian patients with Philadelphia chromosome\u2010negative MPN, including 137 with JAK2 V617F\u2010positive disease and 30 with CALR\u2010mutated disease, and in 97 healthy controls. All subjects had prior high\u2010resolution typing for HLA\u2010A, \u2010B, and \u2010C. Associations between KIR alleles and disease status were evaluated using additive generalized linear models adjusted for age and sex. HLA\u2013KIR receptor\u2013ligand interactions were analyzed using biologically defined interaction models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Several KIR allelic associations with MPN susceptibility were identified, although some involved low\u2010frequency variants. Across analyses, the most consistent finding was that inhibitory KIR2DL2, together with HLA\u2010C2 ligands, was associated with increased susceptibility to MPN overall and within mutation\u2010defined subgroups, with the strongest signal observed in CALR\u2010mutated disease. In contrast, the absence of KIR2DL2 was associated with a lower risk in both JAK2 V617F\u2010positive and CALR\u2010mutated MPN. These findings are consistent with a model in which inherited inhibitory NK\u2010cell signaling may influence early immune escape of emerging mutant clones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inherited variation in KIR genes and HLA\u2013KIR inhibitory interactions may contribute to susceptibility to Philadelphia chromosome\u2010negative MPN. The findings support a possible role for NK\u2010cell regulatory pathways in early MPN pathogenesis, but should be considered hypothesis\u2010generating and require validation in larger independent cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The author has confirmed clinical trial registration is not needed for this submission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jha2.70341","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:11:38Z","timestamp":1783527098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibitory HLA\u2010C\/KIR2DL2 Interactions and KIR Allelic Polymorphisms Are Associated With Susceptibility to Philadelphia Chromosome\u2010Negative Myeloproliferative Neoplasms"],"prefix":"10.1002","volume":"7","author":[{"given":"Velizar","family":"Shivarov","sequence":"first","affiliation":[{"name":"Department of Experimental Research Medical University Pleven  Pleven Bulgaria"},{"name":"Department of Clinical Hematology St. Sophia General Hospital  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergana","family":"Tsvetkova","sequence":"additional","affiliation":[{"name":"Department of Clinical Hematology Alexandrovska University Hospital Medical University Sofia  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgueniy","family":"Hadjiev","sequence":"additional","affiliation":[{"name":"Department of Clinical Hematology Alexandrovska University Hospital Medical University Sofia  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Alexandrovska University Hospital Medical University Sofia  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017578"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba4380"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2020.09.200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1427810"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1240678"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025028642"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.637420"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0052-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174400"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bict.2026.100038"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.70341","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jha2.70341","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.70341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:43:27Z","timestamp":1791603807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.70341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jha2.70341"],"URL":"https:\/\/doi.org\/10.1002\/jha2.70341","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2026-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70341"}}