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Updated: Aug 9, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence

Abhik Datta1, Marcia Bellon, Uma Sinha-Datta

  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, 3025 Wahl Hall West, 3901 Rainbow Blvd, Kansas City, 66160, USA.

Blood
|March 30, 2006
PubMed

Insights

Azidothymidine (AZT) induces cancer cell death by shortening telomeres and activating tumor suppressors. Response to AZT treatment in Adult T-cell leukemia/lymphoma depends on p53 gene status.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Azidothymidine (AZT), an antiviral drug, is used for virus-associated cancers, but its mechanism and treatment failure reasons are unclear.
  • Adult T-cell leukemia/lymphoma (ATL) is an aggressive cancer with a poor prognosis.
  • Understanding AZT's action is crucial for improving ATL treatment outcomes.

Purpose of the Study:

  • To elucidate the mechanism of AZT action in Adult T-cell leukemia/lymphoma (ATL).
  • To investigate the role of p53 in AZT treatment response and resistance in ATL.

Main Methods:

  • In vitro and in vivo studies of T-cell leukemia virus I-infected cells and ATL patients.
  • Analysis of telomerase activity, telomere length, p14ARF, p53, p21Waf1, and p27kip1 expression.
  • Correlation of p53 mutation status with treatment response and disease relapse.

Main Results:

  • AZT treatment inhibited telomerase activity and caused telomere shortening.
  • AZT increased p14ARF expression, leading to p53 stabilization and reactivation.
  • Wild-type p53 ATL patients achieved remission, while mutated p53 patients did not respond, with relapse linked to p53 mutations.

Conclusions:

  • AZT induces cellular senescence and tumor cell death in ATL via telomere shortening and p53 pathway activation.
  • p53 status is a critical determinant of AZT efficacy in ATL.
  • Targeting the p53 pathway may enhance AZT effectiveness in ATL treatment.

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