The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies

Abstract

Deregulation of Polo-like kinase (PLK) transcription via promoter methylation results in perturbations at the protein level, which has been associated with oncogenesis. Our objective was to further characterize the methylation profile for PLK1–4 in bone marrow aspirates displaying blood neoplasms as well as in cells grown in vitro. Clinically, we have determined that more than 70% of lymphoma and myelodysplastic syndrome (MDS)/leukemia bone marrow extracts display a hypermethylated PLK4 promoter region in comparison to the normal. Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. In vitro examination of the PLKs under biologically relevant condition of 5% O₂ revealed that the highly conserved PLKs respond to lower oxygen tension at both the DNA and the protein level. These findings suggest that PLK promoter methylation status correlates with disease and tumorigenesis in blood neoplasms and could serve as a biomarker.

Keywords::

• Polo-like kinases
• epigenetics
• cancer
• hematology
• methylation
• cell cycle

Acknowledgements

We would like to thank Jesse Gardner-Costa for help with incorporating appropriate statistical analyses. Also, thanks go to Anna Kozarova for thorough review of the manuscript and figures.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This research was funded by grants obtained from the Seeds4Hope, Windsor Essex County Cancer Centre Foundation and the National Science and Research Council of Canada, (NSERC, grant #298476-2010).

Supplementary material available online

Supplementary Tables showing further data.