Canonical Wnt/β-catenin signaling pathway is dysregulated in patients with primary and secondary myelofibrosis

Lucijanić, Marko and Livun, Ana and Tomasović-Lončarić, Čedna and Štoos-Veić, Tajana and Pejša, Vlatko and Jakšić, Ozren and Prka, Željko and Kušec, Rajko (2016) Canonical Wnt/β-catenin signaling pathway is dysregulated in patients with primary and secondary myelofibrosis. Clinical Lymphoma Myeloma and Leukemia, 16 (9). pp. 523-256. ISSN 2152-2650

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INTRODUCTION: 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). ----- PATIENTS AND METHODS: 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. ----- RESULTS: 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. ----- CONCLUSION: 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.

Item Type: Article
MeSH: Aged ; Aged, 80 and over ; Biomarkers ; Biopsy ; Bone Marrow/pathology ; Case-Control Studies ; Female ; Fibrosis ; Gene Expression Regulation ; Humans ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Male ; Middle Aged ; Myeloproliferative Disorders/genetics ; Myeloproliferative Disorders/metabolism ; Primary Myelofibrosis/genetics ; Primary Myelofibrosis/metabolism ; Primary Myelofibrosis/pathology ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
Departments: Katedra za internu medicinu
Depositing User: Martina Žužak
Status: Published
Lucijanić, MarkoUNSPECIFIED
Tomasović-Lončarić, ČednaUNSPECIFIED
Štoos-Veić, TajanaUNSPECIFIED
Date: September 2016
Date Deposited: 01 Dec 2017 09:37
Last Modified: 11 Aug 2020 08:50
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