The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms

Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients.

Original languageEnglish
JournalLeukemia and Lymphoma
Volume58
Issue number8
Pages (from-to)1914-1921
ISSN1042-8194
DOIs
Publication statusPublished - Aug 2017

Keywords

  • HLA genes
  • Interferon-alpha2
  • myeloproliferative neoplasms
  • tumor immune surveillance
  • whole blood transcriptional profiling
  • Interferon-alpha/pharmacology
  • Humans
  • Polycythemia Vera/drug therapy
  • Gene Expression Profiling
  • HLA Antigens/genetics
  • Primary Myelofibrosis/drug therapy
  • Thrombocythemia, Essential/drug therapy
  • Myeloproliferative Disorders/drug therapy
  • Alleles
  • Gene Expression Regulation/drug effects

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