Carreño-Tarragona, GonzaloTiana, MaríaRouco, RaquelLeivas, AlejandraVictorino, JesúsGarcía-Vicente, RobertoChase, Andrew J.Maidana, AndreaTapper, William J.Ayala, RosaCross, Nicholas C.P.Martínez-López, JoaquínManzanares, Miguel2026-01-272026-01-272025-05-08Carreño-Tarragona, G, Tiana, M, Rouco, R, Leivas, A, Victorino, J, García-Vicente, R, Chase, A J, Maidana, A, Tapper, W J, Ayala, R, Cross, N C P, Martínez-López, J & Manzanares, M 2025, 'The JAK2 46/1 haplotype influences PD-L1 expression', Blood, vol. 145, no. 19, pp. 2196-2201. https://doi.org/10.1182/blood.20230237870006-4971PubMedCentral: PMC12105720unpaywall: 10.1182/blood.2023023787https://hdl.handle.net/10641/7548Publisher Copyright: © 2025 American Society of HematologyAlthough described more than a decade ago, the mechanism by which the JAK2 46/1 haplotype increases the risk of developing JAK2-mutated myeloproliferative neoplasms (MPNs) remains unexplained. Inflammation and immunity are linked to MPN development and thus could be relevant to the mechanism by which 46/1 mediates its effect. Here, we show that programmed death-1 receptor ligand (PD-L1) expression is elevated in 46/1 haplotype, both in healthy carriers and in CD34+ cells from patients with MPN. Using circular chromosome conformation capture, we observed that PD-L1 and the neighboring PD-L2 loci physically interact with JAK2 in a manner that differs between 46/1 and nonrisk haplotypes. CRISPR/Cas9 genome editing identified a region within JAK2 intron 2 that influences both JAK2 and PD-L1 expression. We suggest that increased PD-L1 expression may be relevant to the mechanism by which 46/1 leads to an increased inherited risk of developing MPN.61849096enghttp://creativecommons.org/licenses/by-nc-nd/4.0/BiochemistryImmunologyHematologyCell BiologyJournal ArticleYesyesjournal articleopen access10.1182/blood.2023023787https://www.scopus.com/pages/publications/105000741930https://www.scopus.com/pages/publications/105000741930#tab=citedBy