title: The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms.
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.
authors.affiliation: a Department of Hematology , Zealand University Hospital , Roskilde , Denmark.
authors.forename: Vibe
authors.initials: V
authors.lastname: Skov
authors.affiliation: a Department of Hematology , Zealand University Hospital , Roskilde , Denmark.|b Center for Cancer Immune Therapy, Department of Hematology , Herlev Hospital, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Caroline Hasselbalch
authors.initials: CH
authors.lastname: Riley
authors.affiliation: c Department of Clinical Genetics , Odense University Hospital , Odense , Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.affiliation: a Department of Hematology , Zealand University Hospital , Roskilde , Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Kjær
authors.affiliation: d Department of Hematology X , Odense University Hospital , Odense , Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stauffer Larsen
authors.affiliation: e Department of Hematology L , Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Ole Weis
authors.initials: OW
authors.lastname: Bjerrum
authors.affiliation: c Department of Clinical Genetics , Odense University Hospital , Odense , Denmark.
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
authors.affiliation: a Department of Hematology , Zealand University Hospital , Roskilde , Denmark.
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000483:Alleles; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics*; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000235:genetics
chemical_list: D006680:HLA Antigens; D016898:Interferon-alpha
keywords: HLA genes; Interferon-alpha2; myeloproliferative neoplasms; tumor immune surveillance; whole blood transcriptional profiling