Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation.
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.
Department of Hematology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark.
Hans Carl
HC
Hasselbalch
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Vibe
V
Skov
Department of Hematology X, Odense University Hospital, Odense, Denmark.
Thomas
T
Stauffer Larsen
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Mads
M
Thomassen
Department of Hematology L, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Caroline
C
Hasselbalch Riley
Department of Hematology L, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Morten K
MK
Jensen
Department of Hematology L, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Ole Weis
OW
Bjerrum
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Torben A
TA
Kruse
D016022:Case-Control Studies; D016000:Cluster Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D011087:Polycythemia Vera / Q000097:blood / Q000235:genetics; D055728:Primary Myelofibrosis / Q000097:blood* / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000097:blood / Q000235:genetics