Clinical features of detection of rare BCR-ABL kinase domain mutations and their response to therapy
| Clinical feature . | Mutations . |
|---|---|
| Mutations arising in CML chronic or accelerated phase | |
| Arising with intermittent imatinib treatment | M237V, Y257C, L273M, E279K, E292K, E292V, I293V, S348L, L364I, V422I, W423R, Y435C, E450K, F486S |
| Arising after nilotinib (no prior imatinib)* | K378R |
| Arising after dasatinib (no prior imatinib)* | R473Q |
| Mutation regressed followed imatinib dose escalation (or major molecular response) | V260A, E292V, I293V, G303E, W423R, Y435C |
| Mutation regressed after switch of TKI (or major molecular response) | E292K, E292Q, E292V, L298V, V304A, L364I, M388L, L411P, I418T, V422I, A433T, L452P, F486S, T495R, M496I |
| No regression after switch to a new TKI (see supplemental Table 1) | N311S (bosutnib + nilotinib), S348L (dasatinib) |
| Mutations arising in CML blast phase or relapsed Ph+ ALL | |
| At relapse of Ph+ ALL | V338G, E450G (along with T315I) |
| At CML blast transformation | E279K (myeloid blasts), A337P (T-cell blasts), L364I (along with T315I, B-cell blasts), V379I |
| Clinical feature . | Mutations . |
|---|---|
| Mutations arising in CML chronic or accelerated phase | |
| Arising with intermittent imatinib treatment | M237V, Y257C, L273M, E279K, E292K, E292V, I293V, S348L, L364I, V422I, W423R, Y435C, E450K, F486S |
| Arising after nilotinib (no prior imatinib)* | K378R |
| Arising after dasatinib (no prior imatinib)* | R473Q |
| Mutation regressed followed imatinib dose escalation (or major molecular response) | V260A, E292V, I293V, G303E, W423R, Y435C |
| Mutation regressed after switch of TKI (or major molecular response) | E292K, E292Q, E292V, L298V, V304A, L364I, M388L, L411P, I418T, V422I, A433T, L452P, F486S, T495R, M496I |
| No regression after switch to a new TKI (see supplemental Table 1) | N311S (bosutnib + nilotinib), S348L (dasatinib) |
| Mutations arising in CML blast phase or relapsed Ph+ ALL | |
| At relapse of Ph+ ALL | V338G, E450G (along with T315I) |
| At CML blast transformation | E279K (myeloid blasts), A337P (T-cell blasts), L364I (along with T315I, B-cell blasts), V379I |
Both mutations regressed in retesting at 6 months after continued nilotinib or dasatinib therapy.