Gleevec Resistance
Development of insensitivity to imatinib (Gleevec) therapy in chronic myeloid leukemia or gastrointestinal stromal tumors, often due to kinase domain mutations.
Full Definition
Gleevec resistance refers to the acquisition of insensitivity to imatinib mesylate (Gleevec), a targeted therapy that inhibits BCR-ABL kinase in chronic myeloid leukemia and KIT/PDGFRA kinases in gastrointestinal stromal tumors. Resistance can be primary (present at diagnosis) or acquired (developing during treatment). The most common mechanism involves mutations in the kinase domain that reduce drug binding affinity, such as the T315I mutation in BCR-ABL. Other mechanisms include gene amplification, alternative pathway activation, or drug efflux. Recognition of resistance patterns has led to the development of second- and third-generation tyrosine kinase inhibitors with activity against resistant clones.
Usage
Usage note: Gleevec is a trademark and should be capitalized; generic name imatinib may be preferred in some contexts.
In Context
- "Molecular analysis revealed T315I mutation as the mechanism of Gleevec resistance in this CML patient." — Laboratory report
- "The development of Gleevec resistance necessitated switching to a second-generation tyrosine kinase inhibitor." — Treatment summary