BCR-ABL kinase domain 돌연변이와 imatinib 내성
Reference: Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia (Cancer Cell, 2002)
https://www.cell.com/cancer-cell/fulltext/S1535-6108(02)00096-X
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chro
Through sequencing analysis of blood or bone marrow samples from patients with chronic myeloid leukemia, we identified BCR-ABL kinase domain mutations in 29 of 32 patients whose disease relapsed after an initial response to the tyrosine kinase inhibitor im
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- Kinase domain mutations are detected in 90% of CML drug binding without significantly affecting the binding of ATP patients who relapse after responding to imatinib.
-Mutant BCR-ABL alleles show varying degree not been previously documented. We next asked if detection of imatinib resistance in vitro,
-Potential predictive value of mutation detection mic instability. in patients with stable disease.
-Evidence for clonal selection of preexisting BCR-ABL kinase domain mutations.
A: imatinib이 부착하는 ABL kinase domain
B: ABL의 P-loop 모양의 비교 (imatinib vs active insulin receptor kinase)
C: 돌연변이로 인한 loop 활성화 -> conformational changes 일어난 모습
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