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

Scientific paper - Original scientific paper

• Author: Marko Lucijanić
• Author: Ana Livun
• Author: Čedna Tomasović-Lončarić
• Author: Tajana Štoos-Veić
• Author: Vlatko Pejša
• Author: Ozren Jakšić
• Author: Željko Prka
• Author: Rajko Kušec
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

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.

• Keywords (english): 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
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Clinical Lymphoma Myeloma and Leukemia
• Numbering: vol. 16, no. 9, pp. 523-256
• p-ISSN: 2152-2650
• DOI: https://doi.org/10.1016/j.clml.2016.06.004
• URN:NBN: urn:nbn:hr:105:690434
• Publication: 2016-09
• Document URL: https://doi.org/10.1016/j.clml.2016.06.004
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 08:57:46