Table 1.
Most frequent BCR-ABL1 mutation and the sensitivity degree to the approved TKIs.
| BCR-ABL1 Mutation | Location $ | Imatinib | Dasatinib | Nilotinib | Bosutinib | Ponatinib | Asciminib |
|---|---|---|---|---|---|---|---|
| Wild-type | Sen | Sen | Sen | Sen | Sen | Sen | |
| M244 | P-loop | Sen | Sen | Sen | Sen | Sen | Sen |
| L248 | P-loop | Int | Int | Sen | Int | Sen | Sen |
| G250 | P-loop | Res | Sen | Int | Res | Sen | Sen |
| Q252 | P-loop | Int | Int | Sen | Sen | Sen | Sen |
| Y253 § | P-loop | Res | Sen | Res | Sen | Sen | Sen |
| E255 § | P-loop | Res | Int | Res | Int | Int | Sen |
| V299 | C-helix | Res | Res | Sen | Res | Sen | Sen |
| T315 ‡, § | Drug contact site | Res | Res | Res | Res | Int | Sen |
| F317 ‡ | Drug contact site | Int | Res | Sen | Int | Sen | Sen |
| A337 | C-loop | Sen | Sen | Sen | Sen | Sen | Int |
| M351 | C-loop | Sen | Sen | Sen | Sen | Sen | Sen |
| M355 | C-loop | Int | Sen | Sen | Sen | Sen | Sen |
| F359 § | C-loop | Int | Sen | Res | Sen | Sen | Sen |
| H396 | A-loop | Int | Sen | Int | Sen | Int | Sen |
| W464 | Myristate pocket | Sen | Sen | Sen | Sen | Sen | Res |
| P465 | Myristate pocket | Sen | Sen | Sen | Sen | Sen | Res |
| V468 | Myristate pocket | Sen | Sen | Sen | Sen | Sen | Res |
| I502 | Myristate pocket | Sen | Sen | Sen | Sen | Sen | Res |
‡ Gatekeeper residue; § Most commonly associated with disease progression and relapse; $ Location of altered amino acid on BCR-ABL protein, P-loop: ATP-binding loop; C-loop: catalytic loop; A-loop: activation loop; Sen: sensitive; Int: intermediate sensitivity; Res: resistant. Data derived from the following references: [27,32,34,35].