Abstract
The majority of patients with chronic phase chronic myeloid leukaemia (CP-CML) treated with imatinib achieves cytogenetic disease remission. Molecular monitoring for residual disease has prognostic significance: rising BCR-ABL levels may provide earliest indication that a patient has become resistant to treatment. The emergence of resistance to imatinib has dampened the enthusiasm for this drug. The most common cause of resistance is the selection of leukemic clones mutated in ABL kinase domain due to amino acid substitutions with prevention of appropriate binding of the drug. Amplification and over-expression of BCR-ABL, acquired cytogenetic aberrations and modulation of drug efflux or influx transporters have been reported. These observations have established the rationale for the creation of new compounds that have been explored in clinical trials. This review will discuss the underlying mechanisms of imatinib-resistance and new strategies to avoid and overcome this phenomenon.
Keywords: Chronic myeloid leukaemia, resistance, imatinib, nilotinib, dasatinib, bosutinib
Cardiovascular & Hematological Disorders-Drug Targets
Title: Resistance to Imatinib in Chronic Myeloid Leukemia and Therapeutic Approaches to Circumvent the Problem
Volume: 9 Issue: 1
Author(s): Massimo Breccia and Giuliana Alimena
Affiliation:
Keywords: Chronic myeloid leukaemia, resistance, imatinib, nilotinib, dasatinib, bosutinib
Abstract: The majority of patients with chronic phase chronic myeloid leukaemia (CP-CML) treated with imatinib achieves cytogenetic disease remission. Molecular monitoring for residual disease has prognostic significance: rising BCR-ABL levels may provide earliest indication that a patient has become resistant to treatment. The emergence of resistance to imatinib has dampened the enthusiasm for this drug. The most common cause of resistance is the selection of leukemic clones mutated in ABL kinase domain due to amino acid substitutions with prevention of appropriate binding of the drug. Amplification and over-expression of BCR-ABL, acquired cytogenetic aberrations and modulation of drug efflux or influx transporters have been reported. These observations have established the rationale for the creation of new compounds that have been explored in clinical trials. This review will discuss the underlying mechanisms of imatinib-resistance and new strategies to avoid and overcome this phenomenon.
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Cite this article as:
Breccia Massimo and Alimena Giuliana, Resistance to Imatinib in Chronic Myeloid Leukemia and Therapeutic Approaches to Circumvent the Problem, Cardiovascular & Hematological Disorders-Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/187152909787581363
DOI https://dx.doi.org/10.2174/187152909787581363 |
Print ISSN 1871-529X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-4063 |
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