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

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...

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Published inLeukemia & 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
LanguageEnglish
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
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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% 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.
AbstractList 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.
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.
Author Ward, Alejandra
Hamm, Caroline
Sivakumar, Gayathri
Kanjeekal, Sindu
Labute, Brayden C.
Shum, David
Hudson, John W.
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Keywords Polo-like kinases
hematology
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cell cycle
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Snippet Deregulation of Polo-like kinase (PLK) transcription via promoter methylation results in perturbations at the protein level, which has been associated with...
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SubjectTerms 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
Title The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies
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