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Leukemic cells with increased telomerase activity exhibit resistance to imatinib

Osamu Yamada1, Kiyotaka Kawauchi, Masaharu Akiyama

  • 1Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan. yamadao@lab.twmu.ac.jp

Leukemia & Lymphoma
|June 24, 2008
PubMed

Insights

Imatinib significantly reduces telomerase activity in chronic myeloid leukemia (CML) cells by directly impacting human telomerase reverse transcriptase (hTERT) transcription. This finding reveals a new antitumor mechanism for imatinib and suggests potential for anti-telomerase therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • Imatinib (Gleevec) is a standard treatment for chronic myeloid leukemia (CML).
  • The precise mechanism by which imatinib exerts its antitumor effects, particularly concerning telomerase, remains unclear.
  • Telomerase plays a crucial role in cancer cell proliferation and survival.

Purpose of the Study:

  • To investigate the impact of imatinib on telomerase activity and human telomerase reverse transcriptase (hTERT) expression in CML.
  • To determine if telomerase inhibition contributes to imatinib's antitumor effects.
  • To elucidate the mechanism of imatinib-induced telomerase suppression.

Main Methods:

  • Treatment of K562 cells and primary leukemic cells with imatinib.
  • Assay of telomerase activity.
  • Measurement of hTERT gene expression.
  • Analysis of cell death rates.

Main Results:

  • Imatinib significantly down-regulated telomerase activity in both K562 and primary CML cells.
  • Leukemic cells from CML patients in blastic crisis exhibited less telomerase suppression compared to those in chronic phase.
  • Inhibition of telomerase was attributed to direct suppression of hTERT transcription, not increased cell death.

Conclusions:

  • Imatinib exerts its antitumor effects, in part, by directly inhibiting hTERT transcription and reducing telomerase activity.
  • This study uncovers a novel mechanism of action for imatinib in CML treatment.
  • Findings support the development of novel anti-telomerase therapies and enhance understanding of telomerase regulation in leukemia.

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