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Association details:
| Biomarker: | BCR-ABL1 Y253H |
|---|---|
| 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:
Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)–based mutagenesis screen: high efficacy of drug combinations
Excerpt:
Overall, these data indicate that the ENU-based assay faithfully reproduces the spectrum of mutations seen in patients with clinical resistance to imatinib mesylate...Spectrum and frequency of BCR-ABL kinase domain mutations recovered in the presence of imatinib mesylate, nilotinib, and dasatinib...Although both dasatinib and nilotinib are much more potent than imatinib mesylate and have activity against most kinase domain mutants, it is conceivable that their specific modes of binding to Abl may lead to new “vulnerable” sites that could confer drug resistance.
DOI:
10.1182/blood-2006-02-004580
