Canonical Wnt/β-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis

Clin Lymphoma Myeloma Leuk. 2016 Sep;16(9):523-526. doi: 10.1016/j.clml.2016.06.004. Epub 2016 Jun 8.

Abstract

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: JAK2 V617F; Philadelphia chromosome-negative myeloproliferative neoplasm; RT PCR; anemia; fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Biomarkers
  • Wnt Proteins
  • beta Catenin
  • Janus Kinase 2