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Published data suggest that <jats:italic>JAK2<\/jats:italic>\u2010V617F\u2010mutated MPN cells express the resistance\u2010related checkpoint PD\u2010L1. By applying RNA\u2010sequencing on granulocytes of 113 MPN patients, we demonstrate that PD\u2010L1 expression is highest among polycythemia vera patients and that PD\u2010L1 expression correlates with <jats:italic>JAK2<\/jats:italic>\u2010V617F mutational burden (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.52; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Single nucleotide polymorphism (SNP) arrays showed that chromosome 9p uniparental disomy (UPD) covers both <jats:italic>PD\u2010L1<\/jats:italic> and <jats:italic>JAK2<\/jats:italic> in all MPN patients examined. MPN cells in <jats:italic>JAK2<\/jats:italic>\u2010V617F\u2010positive patients expressed higher levels of PD\u2010L1 if 9p UPD was present compared to when it was absent (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Moreover, haplotype\u2010based association analyses provided evidence for germline genetic factors at <jats:italic>PD\u2010L1<\/jats:italic> locus contributing to MPN susceptibility independently of the previously described GGCC risk haplotype. We also found that PD\u2010L1 is highly expressed on putative CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>\u2212<\/jats:sup> disease\u2010initiating neoplastic stem cells (NSC) in both <jats:italic>JAK2<\/jats:italic> and <jats:italic>CALR<\/jats:italic>\u2010mutated MPN. PD\u2010L1 overexpression decreased upon exposure to JAK2 blockers and BRD4\u2010targeting agents, suggesting a role for JAK2\u2010STAT5\u2010signaling and BRD4 in PD\u2010L1 expression. Whether targeting of PD\u2010L1 can overcome NSC resistance in MPN remains to be elucidated in forthcoming studies.<\/jats:p>","DOI":"10.1002\/ajh.26461","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:33:12Z","timestamp":1641911592000},"page":"390-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>PD\u2010L1<\/scp> overexpression correlates with <scp><i>JAK2<\/i>\u2010V617F<\/scp> mutational burden and is associated with 9p uniparental disomy in myeloproliferative neoplasms"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-3298","authenticated-orcid":false,"given":"Jelena D.","family":"Milosevic Feenstra","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Hematology and Oncology Medical University of Vienna  Vienna 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