A 7-gene signature depicts the biochemical profile of early prefibrotic myelofibrosis

Research output: Contribution to journalArticle

Abstract

Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to theWorld Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between themmay be challenging and several studies have not been able to distinguish between them.Most lately, it has been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH.Whole blood gene expression profiling was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100%and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, andMMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful tool to differentiate between genuine ET and prePMF but needs to be validated in a larger cohort of "ET" patients.

Details

Authors
  • Vibe Skov
  • Mark Burton
  • Mads Thomassen
  • Thomas Stauffer Larsen
  • Caroline H. Riley
  • Ann Brinch Madelung
  • Lasse Kjær
  • Henrik Bondo
  • Inger Stamp
  • Mats Ehinger
  • Rasmus Dahl-Sørensen
  • Nana Brochmann
  • Karsten Nielsen
  • Jürgen Thiele
  • Morten K. Jensen
  • Ole Weis Bjerrum
  • Torben A. Kruse
  • Hans Carl Hasselbalch
Organisations
External organisations
  • Zealand University Hospital
  • Odense University Hospital
  • Naestved Hospital
  • Aarhus University
  • University of Cologne
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology
Original languageEnglish
Article numbere0161570
JournalPLoS ONE
Volume11
Issue number8
Publication statusPublished - 2016 Aug 1
Publication categoryResearch
Peer-reviewedYes