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Imatinib resistance: obstacles and opportunities.
1Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. litzow.mark@mayo.edu
Archives of Pathology & Laboratory Medicine
|May 11, 2006
Summary
Resistance to imatinib mesylate (IM) in chronic myelogenous leukemia (CML) can occur due to BCR-ABL1 mutations. New SRC and ABL1 inhibitors show promise for overcoming IM resistance in CML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chronic myelogenous leukemia (CML) is driven by the BCR-ABL1 tyrosine kinase.
- Imatinib mesylate (IM) revolutionized CML treatment, inducing high remission rates.
- Therapeutic resistance to IM has emerged as a significant clinical challenge.
Purpose of the Study:
- To review the current status of imatinib mesylate resistance in CML.
- To identify obstacles and opportunities related to IM resistance.
Main Methods:
- A MEDLINE search was conducted for studies from 1950 to 2004.
- Relevant information from selected studies was abstracted and summarized.
Main Results:
- BCR-ABL1 mutations in the kinase domain are the primary mechanism of IM resistance.
- These mutations alter the binding affinity of IM to BCR-ABL1.
- New combined SRC and ABL1 inhibitors are effective against most IM-resistant BCR-ABL1 mutations.
Conclusions:
- Understanding BCR-ABL1 has transformed CML treatment.
- While IM is effective, resistance necessitates alternative therapies.
- Emerging therapies offer hope for controlling or curing CML with low-toxicity oral agents.