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Review ArticleReview

Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib

Michael W. N. Deininger and Brian J. Druker
Pharmacological Reviews September 2003, 55 (3) 401-423; DOI: https://doi.org/10.1124/pr.55.3.4
Michael W. N. Deininger
Oregon Health and Science University Cancer Institute, Portland, Oregon
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Brian J. Druker
Oregon Health and Science University Cancer Institute, Portland, Oregon
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Abstract

Chronic myeloid leukemia (CML) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9. The chimerical Bcr-Abl protein expressed by CML cells has constitutive tyrosine kinase activity, which is essential for the pathogenesis of the disease. Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl, has unprecedented efficacy for the treatment of CML. Most patients with early stage disease achieve durable complete hematological and complete cytogenetic remissions, with minimal toxicity. In contrast, responses are less stable in patients with advanced CML. This review highlights the pathogenesis of CML, its clinical features, and the development of imatinib as a specific molecularly targeted therapy. Aspects of disease monitoring and side effects are covered as well as resistance to imatinib and strategies to overcome resistance, such as alternative signal transduction inhibitors and drug combinations. Perspectives for further development are also discussed.

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Pharmacological Reviews: 55 (3)
Pharmacological Reviews
Vol. 55, Issue 3
1 Sep 2003
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Review ArticleReview

Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib

Michael W. N. Deininger and Brian J. Druker
Pharmacological Reviews September 1, 2003, 55 (3) 401-423; DOI: https://doi.org/10.1124/pr.55.3.4

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Review ArticleReview

Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib

Michael W. N. Deininger and Brian J. Druker
Pharmacological Reviews September 1, 2003, 55 (3) 401-423; DOI: https://doi.org/10.1124/pr.55.3.4
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  • Article
    • Abstract
    • I. Introduction
    • II. Pathogenesis of Chronic Myelogenous Leukemia
    • III. Conventional Treatment Options for Chronic Myelogenous Leukemia
    • IV. Imatinib
    • V. Pharmakokinetics
    • VI. Monitoring Patients on Imatinib
    • VII. Imatinib in Drug Combinations
    • VIII. Mechanism of Action
    • IX. Resistance to Imatinib
    • X. Other Novel Agents for the Treatment of Chronic Myelogenous Leukemia
    • XI. Imatinib for the Treatment of Malignancies Other Than Philadelphia-Positive Leukemia
    • XII. Future Perspectives
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
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