Properties of different point mutations
| AMN107-resistant BCR-ABL mutant . | Concentration at recovery, nM . | No. of colonies . | Percentage of total* . | IC50 of AMN107, nM . | IC50 of imatinib mesylate, nM . |
|---|---|---|---|---|---|
| Wild-type | — | — | — | < 10 | 450 |
| K247N | 125 | 1 | 1.16 | 90 | ≈850 |
| L248V | 250 | 1 | 1.16 | 675 | ≈10 000 |
| Q252H | 125 | 2 | 2.32 | 40 | ≈1 300 |
| Y253C | 250 | 8 | 9.30 | 600 | ≈10 000 |
| Y253H | 500 | 7 | 8.14 | 1300 | ≈10 000 |
| E255K | 250 | 3 | 3.49 | 200 | ≈10 000 |
| L273F | 125 | 1 | 1.16 | 51 | 750 |
| E282K | 250 | 2 | 2.32 | 150 | ≈1 550 |
| K285N | 250 | 2 | 2.32 | ≈500 | ≈3 500 |
| V289L | 125 | 1 | 1.16 | 25 | 1 000 |
| E292K | 125 | 1 | 1.16 | 90 | ≈1 500 |
| N297T | 125 | 1 | 1.16 | 30 | 650 |
| T315I | 500 | 11 | 12.79 | ≈8000 | ≈10 000 |
| H375P | 125 | 1 | 1.16 | 50 | 1 100 |
| T406I | 125 | 1 | 1.16 | 80 | ≈1 400 |
| W430L | 125 | 2 | 2.32 | 90 | 800 |
| E431G | 125 | 1 | 1.16 | 35 | ≈650 |
| AMN107-resistant BCR-ABL mutant . | Concentration at recovery, nM . | No. of colonies . | Percentage of total* . | IC50 of AMN107, nM . | IC50 of imatinib mesylate, nM . |
|---|---|---|---|---|---|
| Wild-type | — | — | — | < 10 | 450 |
| K247N | 125 | 1 | 1.16 | 90 | ≈850 |
| L248V | 250 | 1 | 1.16 | 675 | ≈10 000 |
| Q252H | 125 | 2 | 2.32 | 40 | ≈1 300 |
| Y253C | 250 | 8 | 9.30 | 600 | ≈10 000 |
| Y253H | 500 | 7 | 8.14 | 1300 | ≈10 000 |
| E255K | 250 | 3 | 3.49 | 200 | ≈10 000 |
| L273F | 125 | 1 | 1.16 | 51 | 750 |
| E282K | 250 | 2 | 2.32 | 150 | ≈1 550 |
| K285N | 250 | 2 | 2.32 | ≈500 | ≈3 500 |
| V289L | 125 | 1 | 1.16 | 25 | 1 000 |
| E292K | 125 | 1 | 1.16 | 90 | ≈1 500 |
| N297T | 125 | 1 | 1.16 | 30 | 650 |
| T315I | 500 | 11 | 12.79 | ≈8000 | ≈10 000 |
| H375P | 125 | 1 | 1.16 | 50 | 1 100 |
| T406I | 125 | 1 | 1.16 | 80 | ≈1 400 |
| W430L | 125 | 2 | 2.32 | 90 | 800 |
| E431G | 125 | 1 | 1.16 | 35 | ≈650 |
Six mutations, namely L248V, Q252H, Y253C, Y253H, E255K, and T315I, identified here from the screen, have previously been reported in patients with CML receiving imatinib mesylate, and are known to be associated with imatinib mesylate resistance. All double-mutant clones were recovered at 500 nM concentration.
— indicates no recovery.
(no. of individual colonies/total no. of colonies obtained) × 100.