title: A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis.
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 the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may 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, and MMP8, 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.
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Vibe
authors: V
authors: Skov
authors: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Mark
authors: M
authors: Burton
authors: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Mads
authors: M
authors: Thomassen
authors: Department of Hematology X, Odense University Hospital, Odense, Denmark.
authors: Thomas
authors: T
authors: Stauffer Larsen
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Caroline H
authors: CH
authors: Riley
authors: Department of Pathology, Naestved Hospital, Naestved, Denmark.
authors: Ann
authors: A
authors: Brinch Madelung
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Lasse
authors: L
authors: Kjær
authors: Department of Pathology, Naestved Hospital, Naestved, Denmark.
authors: Henrik
authors: H
authors: Bondo
authors: Department of Pathology, Naestved Hospital, Naestved, Denmark.
authors: Inger
authors: I
authors: Stamp
authors: Department of Pathology, Lund University Hospital, Lund, Sweden.
authors: Mats
authors: M
authors: Ehinger
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Rasmus
authors: R
authors: Dahl-Sørensen
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Nana
authors: N
authors: Brochmann
authors: Department of Pathology, University of Aarhus, Aarhus, Denmark.
authors: Karsten
authors: K
authors: Nielsen
authors: Institute of Pathology, University of Cologne, Köln, Germany.
authors: Jürgen
authors: J
authors: Thiele
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Morten K
authors: MK
authors: Jensen
authors: Department of Hematology L, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Ole
authors: O
authors: Weis Bjerrum
authors: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Torben A
authors: TA
authors: Kruse
authors: Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
authors: Hans Carl
authors: HC
authors: Hasselbalch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology