Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies

Zijun Y. Xu-Monette, L. Jeffrey Medeiros, Yong Li, Robert Z. Orlowski, Michael Andreeff, Carlos E. Bueso-Ramos, Timothy C. Greiner, Timothy J. McDonnell, Ken H. Young

Research output: Contribution to journalReview article

99 Scopus citations

Abstract

Mutations of the TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including lymphomas. Tumor suppression by p53 occurs via both transcription-dependent activities in the nucleus by which p53 regulates transcription of genes involved in cell cycle, DNA repair, apoptosis, signaling, transcription, and metabolism; and transcription-independent activities that induces apoptosis and autophagy in the cytoplasm. In lymphoid malignancies, the frequency of TP53 deletions and mutations is lower than in other types of cancer. Nonetheless, the status of TP53 is an independent prognostic factor in most lymphoma types. Dysfunction of TP53 with wild-type coding sequence can result from deregulated gene expression, stability, and activity of p53. To overcome TP53 pathway inactivation, therapeutic delivery of wild-type p53, activation of mutant p53, inhibition of MDM2-mediated degradation of p53, and activation of p53-dependent and -independent apoptotic pathways have been explored experimentally and in clinical trials. We review the mechanisms of TP53 dysfunction, recent advances implicated in lymphomagenesis, and therapeutic approaches to overcoming p53 inactivation.

Original languageEnglish (US)
Pages (from-to)3668-3683
Number of pages16
JournalBlood
Volume119
Issue number16
DOIs
StatePublished - Apr 19 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Xu-Monette, Z. Y., Jeffrey Medeiros, L., Li, Y., Orlowski, R. Z., Andreeff, M., Bueso-Ramos, C. E., Greiner, T. C., McDonnell, T. J., & Young, K. H. (2012). Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood, 119(16), 3668-3683. https://doi.org/10.1182/blood-2011-11-366062