Shift in overall distribution of mutations following sequential TKI therapies
| Mutation . | Amino acid change . | Nucleotide change (cDNA)* . | After imatinib, n = 67 . | After 2nd TKI, n = 77 . | After 3rd TKI . |
|---|---|---|---|---|---|
| M244V | Met to Val | c.1094A>G | 2 | 3 | — |
| K247L | Lys to Leu | c.1103A>G | 1 | 1 | — |
| L248V | Leu to Val | c.1106C>G | 1 | 1 | — |
| G250E | Gly to Glu | c.1113G>A | 12 | 9 | 2 |
| Q252H | Gln to His | c.1120G>T | — | 1 | — |
| Y253F | Tyr to Phe | c.1122A>T | 1 | 2 | — |
| Y253H | Tyr to His | c.1121T>C | 3 | 5 | — |
| E255K | Glu to Lys | c.1127G>A | 3 | 4 | 1 |
| D276G | Asp to Gly | c.1191A>G | 1 | 2 | — |
| L298V | Leu to Val | c.[1256C>G; 1258A>G] | 1 | 1 | — |
| V299L | Val to Leu | c.1259G>C/T | — | 2 | 1 |
| F311I | Phe to Ile | c.1294T>A | 2 | 4 | — |
| T315I | Thr to Ile | c.1308C>T | 10 | 13 | 2 |
| F317L | Phe to Leu | c.1315C>G/A; c.1313T>C | 7 | 9 | 3 |
| M351T | Met to Thr | c.1416T>C | 3 | — | — |
| E355A | Glu to Ala | c.1428A>C | 1 | 1 | — |
| E355G | Glu to Gly | c.1428A>G | 5 | 2 | 1 |
| F359C | Phe to Cys | c.1440T>G | 3 | 4 | 1 |
| F359V | Phe to Val | c.1439T>G | 1 | 3 | — |
| L364I | Leu to Ile | c.1455C>A | 1 | 1 | — |
| H396R | His to Arg | c.1551A>G | 3 | 4 | 2 |
| H396P | His to Pro | c.1551A>C | — | 1 | — |
| A433T | Ala to Thr | c.1658G>A | 1 | — | — |
| E453K | Glu to Lys | c.1721G>A | — | 1 | — |
| E459G | Glu to Gly | c.1740A>G | 1 | 1 | — |
| E459K | Glu to Lys | c.1739G>A | 1 | 1 | — |
| E459Q | Glu to Gln | c.1739G>C | 2 | 1 | — |
| F486S | Phe to Ser | c.1821T>C | 1 | — | — |
| T495R | Thr to Arg | c.1848C>G | — | — | 1 |
| Mutation . | Amino acid change . | Nucleotide change (cDNA)* . | After imatinib, n = 67 . | After 2nd TKI, n = 77 . | After 3rd TKI . |
|---|---|---|---|---|---|
| M244V | Met to Val | c.1094A>G | 2 | 3 | — |
| K247L | Lys to Leu | c.1103A>G | 1 | 1 | — |
| L248V | Leu to Val | c.1106C>G | 1 | 1 | — |
| G250E | Gly to Glu | c.1113G>A | 12 | 9 | 2 |
| Q252H | Gln to His | c.1120G>T | — | 1 | — |
| Y253F | Tyr to Phe | c.1122A>T | 1 | 2 | — |
| Y253H | Tyr to His | c.1121T>C | 3 | 5 | — |
| E255K | Glu to Lys | c.1127G>A | 3 | 4 | 1 |
| D276G | Asp to Gly | c.1191A>G | 1 | 2 | — |
| L298V | Leu to Val | c.[1256C>G; 1258A>G] | 1 | 1 | — |
| V299L | Val to Leu | c.1259G>C/T | — | 2 | 1 |
| F311I | Phe to Ile | c.1294T>A | 2 | 4 | — |
| T315I | Thr to Ile | c.1308C>T | 10 | 13 | 2 |
| F317L | Phe to Leu | c.1315C>G/A; c.1313T>C | 7 | 9 | 3 |
| M351T | Met to Thr | c.1416T>C | 3 | — | — |
| E355A | Glu to Ala | c.1428A>C | 1 | 1 | — |
| E355G | Glu to Gly | c.1428A>G | 5 | 2 | 1 |
| F359C | Phe to Cys | c.1440T>G | 3 | 4 | 1 |
| F359V | Phe to Val | c.1439T>G | 1 | 3 | — |
| L364I | Leu to Ile | c.1455C>A | 1 | 1 | — |
| H396R | His to Arg | c.1551A>G | 3 | 4 | 2 |
| H396P | His to Pro | c.1551A>C | — | 1 | — |
| A433T | Ala to Thr | c.1658G>A | 1 | — | — |
| E453K | Glu to Lys | c.1721G>A | — | 1 | — |
| E459G | Glu to Gly | c.1740A>G | 1 | 1 | — |
| E459K | Glu to Lys | c.1739G>A | 1 | 1 | — |
| E459Q | Glu to Gln | c.1739G>C | 2 | 1 | — |
| F486S | Phe to Ser | c.1821T>C | 1 | — | — |
| T495R | Thr to Arg | c.1848C>G | — | — | 1 |
TKI indicates tyrosine kinase inhibitor; and —, no data.