Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis

Vibe Skov, Thomas Stauffer Larsen, Mads Thomassen, Caroline Hasselbalch Riley, Morten K. Jensen, Ole Weis Bjerrum, Torben A. Kruse, Hans Carl Hasselbalch

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)54-60
Antal sider7
TidsskriftEuropean Journal of Haematology
Vol/bind87
Udgave nummer1
DOI
StatusUdgivet - 1 jul. 2011

Fingeraftryk Udforsk hvilke forskningsemner 'Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis' indeholder.

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