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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1427810
Differential Modulation of Mutant CALR and JAK2 V617F-Driven Oncogenesis by HLA Genotype in Myeloproliferative Neoplasms
Provisionally accepted- 1 Other, Pleven, Bulgaria
- 2 Other, Sofia, Bulgaria
- 3 Other, Varna, Bulgaria
- 4 Department of Physical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria
- 5 Department of Clinical Immunology with Stem Cell Bank, Aleksandrovska University Hospital, Sofia, Bulgaria
It has been demonstrated previously that Human Leukocyte Antigen class I (HLA-I) and class II (HLA-II) 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 HLA genes in CALRmut+ MPNs. High-resolution genotyping of HLA-I and -II loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients, and 1083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one HLA-I allele (C*06:02) 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 presentation capabilities of the HLA-I loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of TAP1 and CIITA genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the HLA-I 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.
Keywords: Immunoediting, HLA, MPN, Mutation, CALR, JAK2 V617F, neoantigen
Received: 08 May 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Shivarov, Tsvetkova, Micheva, Hadjiev, Petrova, Ivanova, Madjarova and Ivanova - Shivarova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Velizar S. Shivarov, Other, Pleven, Bulgaria
Milena I. Ivanova - Shivarova, Department of Clinical Immunology with Stem Cell Bank, Aleksandrovska University Hospital, Sofia, Bulgaria
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