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
C2 - 24454890
SN - 1932-6203
VL - 9
JO - PLOS ONE
JF - PLOS ONE
IS - 1
M1 - e85567
ER -