title: Canonical Wnt/β-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis.
abstract: β-Catenin is a central effector molecule of the canonical wingless-related integration site (Wnt) signaling pathway. It is important for maintenance of stem cell homeostasis and its aberrant activation has been implicated in a wide array of malignant hematological disorders. There are few reports suggesting its dysregulation in Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs).
  
  
  
  We analyzed β-catenin mRNA expression in bone marrow (BM) aspirates of 29 patients with primary (PMF) and 4 patients with secondary, post Ph- MPN, myelofibrosis (SMF) using quantitative real-time polymerase chain reaction (qRT PCR). The control group consisted of 16 BM aspirates from patients with limited-stage aggressive non-Hodgkin lymphoma without BM involvement. We compared relative gene expression with clinical and hematological parameters.
  
  
  
  Relative expression of β-catenin differed significantly among groups (P = .0002), it was significantly higher in patients with PMF and SMF than in the control group, but did not differ between patients with PMF and SMF. A negative correlation was found regarding hemoglobin level in PMF (P = .017). No association according to Janus kinase 2 (JAK2) V617F mutational status or JAK2 V617F allele burden was detected.
  
  
  
  Our results show for the first time that β-catenin mRNA expression is increased in patients with PMF and SMF and its upregulation might potentiate anemia. A number of inflammatory cytokines associated with PMF are capable of mediating their effects through increased β-catenin expression. Accordingly, β-catenin can induce expression of a number of genes implicated in processes of cell cycle control, fibrosis, and angiogenesis, which are central to the PMF pathogenesis. Therefore, β-catenin might represent an interesting new therapeutic target in these diseases.
authors.affiliation: Department of Hematology, University Hospital Dubrava, Zagreb, Croatia. Electronic address: markolucijanic@yahoo.com.
authors.forename: Marko
authors.initials: M
authors.lastname: Lucijanic
authors.affiliation: Clinical Institute of Laboratory Diagnosis, Division of Molecular Diagnosis and Genetics, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Livun
authors.affiliation: Department of Pathology, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Cedna
authors.initials: C
authors.lastname: Tomasovic-Loncaric
authors.affiliation: Department of Clinical Cytology and Cytometry, University Hospital Dubrava, Zagreb, Croatia; University of Osijek, School of Medicine, Osijek, Croatia.
authors.forename: Tajana
authors.initials: T
authors.lastname: Stoos-Veic
authors.affiliation: Department of Hematology, University Hospital Dubrava, Zagreb, Croatia; University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Vlatko
authors.initials: V
authors.lastname: Pejsa
authors.affiliation: Department of Hematology, University Hospital Dubrava, Zagreb, Croatia; University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Ozren
authors.initials: O
authors.lastname: Jaksic
authors.affiliation: Department of Hematology, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Prka
authors.affiliation: Department of Hematology, University Hospital Dubrava, Zagreb, Croatia; University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Rajko
authors.initials: R
authors.lastname: Kusec
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism*; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051153:Wnt Proteins; D051176:beta Catenin; D053614:Janus Kinase 2
keywords: JAK2 V617F; Philadelphia chromosome-negative myeloproliferative neoplasm; RT PCR; anemia; fibrosis