title: Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis.
abstract: Gene expression profiling studies have unraveled deregulation of several genes that might be of pathogenetic importance for the development and phenotype of the Philadelphia-negative chronic myeloproliferative neoplasms. In the context of interferon-alpha2 as a promising therapeutic agent, we focused upon the transcriptional profiling of interferon-associated genes in patients with essential thrombocythemia (ET) (n = 19), polycythemia vera (PV) (n = 41), and primary myelofibrosis (PMF) (n = 9). Using whole-blood transcriptional profiling and accordingly obtaining an integrated signature of genes expressed in several immune cells (granulocytes, monocytes, B cells, T cells, platelets), we have identified a number of interferon-associated genes to be significantly deregulated but with a highly significant deregulation of interferon-inducible gene 27 (IFI27) (ET, PV, and PMF, fold change 8, 16, and 30, respectively). The striking deregulation of IFI genes may reflect a hyperstimulated but insufficient immune system being most enhanced in patients with advanced myelofibrosis, in whom the IFI27 gene displayed an exceedingly high expression. The interferon signature may reflect primary myelofibrosis as the burn-out phase of chronic inflammation which ultimately elicits clonal evolution and expansion owing to an exaggerated but incompetent antitumor immune response. Finally, IFI27 may be a novel biomarker of disease activity and tumor burden in patients with CMPNs.
authors: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Vibe
authors: V
authors: Skov
authors: Thomas Stauffer
authors: TS
authors: Larsen
authors: Mads
authors: M
authors: Thomassen
authors: Caroline Hasselbalch
authors: CH
authors: Riley
authors: Morten K
authors: MK
authors: Jensen
authors: Ole Weis
authors: OW
authors: Bjerrum
authors: Torben A
authors: TA
authors: Kruse
authors: Hans Carl
authors: HC
authors: Hasselbalch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011087:Polycythemia Vera / Q000235:genetics / Q000276:immunology; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000276:immunology*; D012313:RNA / Q000097:blood / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C406887:IFI27 protein, human; D008565:Membrane Proteins; D012313:RNA