Telomere/telomerase interplay in virus-driven and virus-independent lymphomagenesis: Pathogenic and clinical implications

Riccardo Dolcetti, Anita De Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

Telomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus-related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus-unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase.

Original languageEnglish
Pages (from-to)233-253
Number of pages21
JournalMedicinal Research Reviews
Volume32
Issue number2
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Telomerase
  • Telomerase inhibitors
  • Telomere length
  • Virus-driven lymphomagenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Pharmacology

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