title: Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis.
abstract: Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might be down-regulation of major histocompatibility (MHC) class I and II genes, which are used by tumor cells to escape antitumor T-cell-mediated immune responses. We have performed whole blood transcriptional profiling of genes encoding human leukocyte antigen (HLA) class I and II molecules, β2-microglobulin and members of the antigen processing machinery of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). The findings of significant down-regulation of several of these genes may possibly be of major importance for defective tumor immune surveillance. Since up-regulation of HLA genes is recorded during treatment with epigenome modulating agents (DNA-hypomethylators and DNA-hyperacetylators [histone deacetylase inhibitors]) and interferon-α2, our findings call for prospective transcriptional studies of HLA genes during treatment with these agents.
authors.affiliation: Department of Clinical Genetics.
authors.forename: Vibe
authors.initials: V
authors.lastname: Skov
authors.forename: Caroline Hasselbalch
authors.initials: CH
authors.lastname: Riley
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.forename: Thomas Stauffer
authors.initials: TS
authors.lastname: Larsen
authors.forename: Morten K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Ole Weis
authors.initials: OW
authors.lastname: Bjerrum
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II