The development of imatinib as a therapeutic agent for chronic myeloid leukemia

Michael Deininger, Elisabeth Buchdunger, Brian Druker

Research output: Contribution to journalArticle

962 Citations (Scopus)

Abstract

Imatinib has revolutionized drug therapy of chronic myeloid leukemia (CML). Preclinical studies were promising but the results of clinical trials by far exceeded expectations. Responses in chronic phase are unprecedented, with rates of complete cytogenetic response (CCR) of more than 40% in patients after failure of interferon-α (IFN) and more than 80% in newly diagnosed patients, a level of efficacy that led to regulatory approval in record time. While most of these responses are stable, resistance to treatment after an initial response is common in more advanced phases of the disease. Mutations in the kinase domain (KD) of BCR-ABL that impair imatinib binding have been identified as the leading cause of resistance. Patients with CCR who achieve a profound reduction of BCR-ABL mRNA have a very low risk of disease progression. However, residual disease usually remains detectable with reverse transcription-polymerase chain reaction (RT-PCR), indicating that disease eradication may pose a significant challenge. The mechanisms underlying the persistence of minimal residual disease are unknown. In this manuscript, we review the preclinical and clinical development of imatinib for the therapy of CML, resistance and strategies that may help to eliminate resistant or residual leukemia.

Original languageEnglish (US)
Pages (from-to)2640-2653
Number of pages14
JournalBlood
Volume105
Issue number7
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Disease Eradication
Residual Neoplasm
Interferons
Reverse Transcription
Disease Progression
Leukemia
Phosphotransferases
Drug therapy
Therapeutics
Clinical Trials
Polymerase chain reaction
Drug Therapy
Transcription
Polymerase Chain Reaction
Messenger RNA
Mutation
Imatinib Mesylate

ASJC Scopus subject areas

  • Hematology

Cite this

The development of imatinib as a therapeutic agent for chronic myeloid leukemia. / Deininger, Michael; Buchdunger, Elisabeth; Druker, Brian.

In: Blood, Vol. 105, No. 7, 01.04.2005, p. 2640-2653.

Research output: Contribution to journalArticle

Deininger, Michael ; Buchdunger, Elisabeth ; Druker, Brian. / The development of imatinib as a therapeutic agent for chronic myeloid leukemia. In: Blood. 2005 ; Vol. 105, No. 7. pp. 2640-2653.
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