Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies

Nelofer Syed, Paul Smith, Alexandra Sullivan, Lindsay C Spender, Martin Dyer, Lorraine Karran, Jenny O'Nions, Martin Allday, Ingrid Hoffmann, Dorothy Crawford, Beverley Griffin, Paul J Farrell, Tim Crook (Lead / Corresponding author)

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    86 Citations (Scopus)

    Abstract

    The Polo-like kinases (Plks) are a highly conserved family of protein kinases that function in regulation of cell cycle and DNA damage-induced checkpoints. Evidence of a tumor suppressor function for the Plks in human neoplasia is lacking. Here, we report that Snk/Plk2 is transcriptionally down-regulated in B-cell neoplasms. Silencing occurs with very high frequency in Burkitt lymphoma (BL) but is also detected in B-cell neoplasms of other types and is associated with aberrant cytosine methylation in the CpG island located at the 5' end of the SNK/PLK2 gene. Silencing is specific to malignant B cells because SNK/PLK2 was unmethylated (and expressed) in primary B lymphocytes, in EBV-immortalized B lymphoblastoid cell lines (LCLs), and in adenocarcinomas (of the breast) and squamous-cell carcinomas (of the head and neck). Expression of Snk/Plk2 in BL cell lines was restored by demethylating agents. The related PLK1 and PLK3 (FNK/PRK) genes were overexpressed in BL cell lines lacking Snk/Plk2 expression, consistent with functional degeneracy among the Plk family. Ectopic expression of Snk/Plk2 in BL cells resulted in apoptosis, a potential mechanistic basis underlying the strong selective pressure for abrogation of Snk/Plk2 function in B-cell neoplasia.

    Original languageEnglish
    Pages (from-to)250-256
    Number of pages7
    JournalBlood
    Volume107
    Issue number1
    Early online date22 Dec 2005
    DOIs
    Publication statusPublished - 1 Jan 2006

    Keywords

    • Apoptosis
    • B-Lymphocytes
    • Cell Cycle Proteins
    • DNA Methylation
    • Gene Expression Regulation, Neoplastic
    • Gene Silencing
    • Humans
    • Leukemia, B-Cell
    • Lymphoma, B-Cell
    • Protein-Serine-Threonine Kinases
    • Proto-Oncogene Proteins
    • Transcription, Genetic
    • Tumor Cells, Cultured
    • Journal Article
    • Research Support, Non-U.S. Gov't

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  • Cite this

    Syed, N., Smith, P., Sullivan, A., Spender, L. C., Dyer, M., Karran, L., O'Nions, J., Allday, M., Hoffmann, I., Crawford, D., Griffin, B., Farrell, P. J., & Crook, T. (2006). Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Blood, 107(1), 250-256. https://doi.org/10.1182/blood-2005-03-1194