A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

• Published in: PloS one 2016-08, Vol.11 (8), p.e0161570-e0161570
• Main Authors: Skov, Vibe, Burton, Mark, Thomassen, Mads, Stauffer Larsen, Thomas, Riley, Caroline H, Brinch Madelung, Ann, Kjær, Lasse, Bondo, Henrik, Stamp, Inger, Ehinger, Mats, Dahl-Sørensen, Rasmus, Brochmann, Nana, Nielsen, Karsten, Thiele, Jürgen, Jensen, Morten K, Weis Bjerrum, Ole, Kruse, Torben A, Hasselbalch, Hans Carl
• Format: Article
• Language: English
• Subjects: Adhesion tests; Adult; Aged; Aged, 80 and over; Analysis; Anemia; Basic Medicine; Biology and Life Sciences; Biopsy; Blood; Blood tests; Bone marrow; Bone Marrow - metabolism; Bone Marrow - pathology; Cancer and Oncology; Cancer och onkologi; Cell adhesion; Classification; Clinical Medicine; Comparative analysis; Computer and Information Sciences; Cytokines; Dehydrogenases; Diagnosis; Differential diagnosis; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic aspects; Health aspects; Hematology; Histology; Humans; Inflammation; Klinisk medicin; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Leukocytes; Leukocytosis; Male; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicine and Health Sciences; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Myelofibrosis; Neutrophil collagenase; Pathology; Patients; Primary Myelofibrosis - genetics; Primary Myelofibrosis - metabolism; Primary Myelofibrosis - pathology; Principal components analysis; Risk factors; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161570

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.