title: 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.
authors.affiliation: Department of Biology, University of Windsor , Windsor, ON , Canada.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ward
authors.forename: Gayathri
authors.initials: G
authors.lastname: Sivakumar
authors.forename: Sindu
authors.initials: S
authors.lastname: Kanjeekal
authors.forename: Caroline
authors.initials: C
authors.lastname: Hamm
authors.forename: Brayden C
authors.initials: BC
authors.lastname: Labute
authors.forename: David
authors.initials: D
authors.lastname: Shum
authors.forename: John W
authors.initials: JW
authors.lastname: Hudson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C490219:PLK4 protein, human; C496126:PLK2 protein, human
keywords: Polo-like kinases; cancer; cell cycle; epigenetics; hematology; methylation