Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Identifying a distinct gene signature for myelofibrosis may yield novel information of the genes, which are responsible for progression of essential thrombocythemia and polycythemia vera towards myelofibrosis. We aimed at identifying a simple gene signature - composed of a few genes - which were selectively and highly deregulated in myelofibrosis patients. Gene expression microarray studies have been performed on whole blood from 69 patients with myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG, and AZU1), which were highly significantly deregulated in PMF only. None of these genes were significantly regulated in ET and PV patients. However, hierarchical cluster analysis showed that these genes were also highly expressed in a subset of patients with ET (n = 1) and PV (n = 4) transforming towards myelofibrosis and/or being featured by an aggressive phenotype. We have identified a simple 5-gene signature, which is uniquely and highly significantly deregulated in patients in transitional stages of ET and PV towards myelofibrosis and in patients with PMF only. Some of these genes are considered to be responsible for the derangement of bone marrow stroma in myelofibrosis. Accordingly, this gene-signature may reflect key processes in the pathogenesis and pathophysiology of myelofibrosis development.

OriginalsprogEngelsk
Artikelnummere85567
TidsskriftPLOS ONE
Vol/bind9
Udgave nummer1
ISSN1932-6203
DOI
StatusUdgivet - 2014

Fingeraftryk

Blood
Genes
blood
genes
thrombocythemia
polycythemia
Polycythemia Vera
Cluster analysis
Microarrays
pathophysiology
Gene expression
bone marrow
Cluster Analysis
cluster analysis
Bone
pathogenesis
phenotype
gene expression
neoplasms

Citer dette

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title = "Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation",
abstract = "Identifying a distinct gene signature for myelofibrosis may yield novel information of the genes, which are responsible for progression of essential thrombocythemia and polycythemia vera towards myelofibrosis. We aimed at identifying a simple gene signature - composed of a few genes - which were selectively and highly deregulated in myelofibrosis patients. Gene expression microarray studies have been performed on whole blood from 69 patients with myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG, and AZU1), which were highly significantly deregulated in PMF only. None of these genes were significantly regulated in ET and PV patients. However, hierarchical cluster analysis showed that these genes were also highly expressed in a subset of patients with ET (n = 1) and PV (n = 4) transforming towards myelofibrosis and/or being featured by an aggressive phenotype. We have identified a simple 5-gene signature, which is uniquely and highly significantly deregulated in patients in transitional stages of ET and PV towards myelofibrosis and in patients with PMF only. Some of these genes are considered to be responsible for the derangement of bone marrow stroma in myelofibrosis. Accordingly, this gene-signature may reflect key processes in the pathogenesis and pathophysiology of myelofibrosis development.",
keywords = "Case-Control Studies, Cluster Analysis, Disease Progression, Gene Expression Profiling, Gene Expression Regulation, Humans, Polycythemia Vera, Primary Myelofibrosis, Thrombocythemia, Essential",
author = "Hasselbalch, {Hans Carl} and Vibe Skov and {Stauffer Larsen}, Thomas and Mads Thomassen and {Hasselbalch Riley}, Caroline and Jensen, {Morten K} and Bjerrum, {Ole Weis} and Kruse, {Torben A}",
year = "2014",
doi = "10.1371/journal.pone.0085567",
language = "English",
volume = "9",
journal = "P L o S One",
issn = "1932-6203",
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Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation. / Hasselbalch, Hans Carl; Skov, Vibe; Stauffer Larsen, Thomas; Thomassen, Mads; Hasselbalch Riley, Caroline; Jensen, Morten K; Bjerrum, Ole Weis; Kruse, Torben A.

I: PLOS ONE, Bind 9, Nr. 1, e85567, 2014.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation

AU - Hasselbalch, Hans Carl

AU - Skov, Vibe

AU - Stauffer Larsen, Thomas

AU - Thomassen, Mads

AU - Hasselbalch Riley, Caroline

AU - Jensen, Morten K

AU - Bjerrum, Ole Weis

AU - Kruse, Torben A

PY - 2014

Y1 - 2014

N2 - Identifying a distinct gene signature for myelofibrosis may yield novel information of the genes, which are responsible for progression of essential thrombocythemia and polycythemia vera towards myelofibrosis. We aimed at identifying a simple gene signature - composed of a few genes - which were selectively and highly deregulated in myelofibrosis patients. Gene expression microarray studies have been performed on whole blood from 69 patients with myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG, and AZU1), which were highly significantly deregulated in PMF only. None of these genes were significantly regulated in ET and PV patients. However, hierarchical cluster analysis showed that these genes were also highly expressed in a subset of patients with ET (n = 1) and PV (n = 4) transforming towards myelofibrosis and/or being featured by an aggressive phenotype. We have identified a simple 5-gene signature, which is uniquely and highly significantly deregulated in patients in transitional stages of ET and PV towards myelofibrosis and in patients with PMF only. Some of these genes are considered to be responsible for the derangement of bone marrow stroma in myelofibrosis. Accordingly, this gene-signature may reflect key processes in the pathogenesis and pathophysiology of myelofibrosis development.

AB - Identifying a distinct gene signature for myelofibrosis may yield novel information of the genes, which are responsible for progression of essential thrombocythemia and polycythemia vera towards myelofibrosis. We aimed at identifying a simple gene signature - composed of a few genes - which were selectively and highly deregulated in myelofibrosis patients. Gene expression microarray studies have been performed on whole blood from 69 patients with myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG, and AZU1), which were highly significantly deregulated in PMF only. None of these genes were significantly regulated in ET and PV patients. However, hierarchical cluster analysis showed that these genes were also highly expressed in a subset of patients with ET (n = 1) and PV (n = 4) transforming towards myelofibrosis and/or being featured by an aggressive phenotype. We have identified a simple 5-gene signature, which is uniquely and highly significantly deregulated in patients in transitional stages of ET and PV towards myelofibrosis and in patients with PMF only. Some of these genes are considered to be responsible for the derangement of bone marrow stroma in myelofibrosis. Accordingly, this gene-signature may reflect key processes in the pathogenesis and pathophysiology of myelofibrosis development.

KW - Case-Control Studies

KW - Cluster Analysis

KW - Disease Progression

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Humans

KW - Polycythemia Vera

KW - Primary Myelofibrosis

KW - Thrombocythemia, Essential

U2 - 10.1371/journal.pone.0085567

DO - 10.1371/journal.pone.0085567

M3 - Journal article

VL - 9

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 1

M1 - e85567

ER -