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Association details:
| Biomarker: | BCR-ABL1 E459K |
|---|---|
| Cancer: | Chronic Myeloid Leukemia |
| Drug: | imatinib (c-KIT inhibitor, Bcr-abl tyrosine kinase inhibitor, PDGFR inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase
Excerpt:
Mutations were identified in 60 (60%) of these patients (all with imatinib-resistant CML-AP). Among the 60 patients with mutations, 26 unique imatinib-resistant mutations were identified, of which G250E was the most common (n = 9) (Table 5).
DOI:
10.1182/blood-2006-09-046839
Source:
Title:
Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis
Excerpt:
Amino acids 417, 459, and 486 are located at the C-terminal of the kinase domain distant to the imatinib binding site. It is possible that mutation at these sites causes conformational changes to the BCR-ABL protein that alters the equilibrium to the active conformation and impairs imatinib binding....Our data suggest that mutations beyond the activation loop are also implicated in imatinib resistance, and patients with these mutations may benefit from therapeutic intervention.
DOI:
https://doi.org/10.1182/blood-2002-09-2896
