A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis.
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 W...
Main Authors: | , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5007012?pdf=render |
id |
doaj-e8a77e96cb5f4691a2d728bdace4470e |
---|---|
record_format |
Article |
spelling |
doaj-e8a77e96cb5f4691a2d728bdace4470e2020-11-25T02:13:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016157010.1371/journal.pone.0161570A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis.Vibe SkovMark BurtonMads ThomassenThomas Stauffer LarsenCaroline H RileyAnn Brinch MadelungLasse KjærHenrik BondoInger StampMats EhingerRasmus Dahl-SørensenNana BrochmannKarsten NielsenJürgen ThieleMorten K JensenOle Weis BjerrumTorben A KruseHans Carl HasselbalchRecent 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.http://europepmc.org/articles/PMC5007012?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. PLoS ONE |
author_facet |
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 |
author_sort |
Vibe Skov |
title |
A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. |
title_short |
A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. |
title_full |
A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. |
title_fullStr |
A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. |
title_full_unstemmed |
A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis. |
title_sort |
7-gene signature depicts the biochemical profile of early prefibrotic myelofibrosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5007012?pdf=render |
work_keys_str_mv |
AT vibeskov a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT markburton a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT madsthomassen a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT thomasstaufferlarsen a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT carolinehriley a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT annbrinchmadelung a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT lassekjær a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT henrikbondo a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT ingerstamp a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT matsehinger a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT rasmusdahlsørensen a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT nanabrochmann a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT karstennielsen a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT jurgenthiele a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT mortenkjensen a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT oleweisbjerrum a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT torbenakruse a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT hanscarlhasselbalch a7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT vibeskov 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT markburton 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT madsthomassen 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT thomasstaufferlarsen 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT carolinehriley 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT annbrinchmadelung 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT lassekjær 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT henrikbondo 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT ingerstamp 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT matsehinger 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT rasmusdahlsørensen 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT nanabrochmann 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT karstennielsen 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT jurgenthiele 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT mortenkjensen 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT oleweisbjerrum 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT torbenakruse 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis AT hanscarlhasselbalch 7genesignaturedepictsthebiochemicalprofileofearlyprefibroticmyelofibrosis |
_version_ |
1724905771189141504 |