{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:10:40Z","timestamp":1793070640771,"version":"4.5.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>It has been demonstrated previously that human leukocyte antigen class I (<jats:italic>HLA-I<\/jats:italic>) and class II (<jats:italic>HLA-II<\/jats:italic>) alleles may modulate JAK2 V617F and CALR mutation (CALRmut)-associated oncogenesis in myeloproliferative neoplasms (MPNs). However, the role of immunogenetic factors in MPNs remains underexplored. We aimed to investigate the potential involvement of <jats:italic>HLA<\/jats:italic> genes in CALRmut+ MPNs. High-resolution genotyping of <jats:italic>HLA-I<\/jats:italic> and <jats:italic>-II<\/jats:italic> loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients and 1,083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one <jats:italic>HLA-I<\/jats:italic> allele (<jats:italic>C*06:02<\/jats:italic>) showed an inverse correlation with presence of CALR mutation. A meta-analysis across independent cohorts and healthy individuals from the 1000 Genomes Project confirmed an inverse correlation between the presentation capabilities of the <jats:italic>HLA-I<\/jats:italic> loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of <jats:italic>TAP1<\/jats:italic> and <jats:italic>CIITA<\/jats:italic> genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the <jats:italic>HLA-I<\/jats:italic> genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1427810","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:29:16Z","timestamp":1726460956000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential modulation of mutant CALR and JAK2 V617F-driven oncogenesis by HLA genotype in myeloproliferative 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