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Related Experiment Videos

CML clonal evolution with resistance to single agent imatinib therapy.

R Swords1, J Quinn, M Fay

  • 1Department of Haematology, Beaumont Hospital, Dublin, Ireland. ronanswords@yahoo.co.uk

Clinical and Laboratory Haematology
|September 24, 2005
PubMed
Summary

This case study shows that combining imatinib mesylate with cytarabine can effectively manage chronic myeloid leukemia (CML) that is resistant to imatinib alone. This combination therapy helped revert clonal evolution and achieve a better cytogenetic response in a CML patient.

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome.
  • Standard initial therapies include tyrosine kinase inhibitors like imatinib mesylate.
  • Resistance to single-agent therapy can lead to disease progression and clonal evolution.

Observation:

  • A 58-year-old male with CML showed no cytogenetic response to interferon-alpha and hydroxyurea.
  • Subsequent imatinib mesylate treatment also failed to elicit a cytogenetic response.
  • The patient developed complex clonal evolution, including an additional Philadelphia chromosome and trisomy 8.

Findings:

  • Adding cytarabine to imatinib mesylate treatment resulted in reversion to single Philadelphia chromosome positivity.

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  • The additional clonal abnormalities (trisomy 8) disappeared with combination therapy.
  • This suggests a synergistic effect of imatinib and cytarabine in overcoming resistance.

    • Implications:

    • Combined imatinib and cytarabine therapy is a viable strategy for managing imatinib-resistant CML.
    • Understanding clonal evolution is crucial for tailoring CML treatment regimens.
    • This approach may offer a new therapeutic option for patients with refractory CML.