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

• Published in: Leukemia & lymphoma Vol. 56; no. 7; pp. 2123 - 2133
• Main Authors: Ward, Alejandra, Sivakumar, Gayathri, Kanjeekal, Sindu, Hamm, Caroline, Labute, Brayden C., Shum, David, Hudson, John W.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.07.2015
• Subjects: Biomarkers, Tumor - genetics; cancer; cell cycle; Cell Cycle Proteins - genetics; DNA Methylation; Epigenesis, Genetic; epigenetics; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Hematologic Neoplasms - diagnosis; Hematologic Neoplasms - genetics; hematology; Humans; methylation; Polo-Like Kinase 1; Polo-like kinases; Prognosis; Promoter Regions, Genetic - genetics; Protein Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins - genetics; Real-Time Polymerase Chain Reaction; Tumor Cells, Cultured; Tumor Suppressor Proteins; Polo-like kinases; hematology; cancer; cell cycle; methylation; epigenetics
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2014.971407

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% O 2 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.