Table 1.
List of the non-clonal mutations identified in the BCR-ABL1 fusion gene from imatinib-resistant K562 clones
| Samples | Position | AA change | Codon change | Sequence context |
|---|---|---|---|---|
| 1,503 | E495G | GAA > GGA | ||
| Control | 1,472 | R491Q | CGG > CAG | GCCGG |
| 1,503 | Silent | TTT > TTC | ||
| 633 | G100C | GGC > TGC | GCCTA | |
| AID | 395 | Silent | AAA > AAG | |
| 568 | G190D | GGC > GAC | TGCCA | |
| 633 | T212A | ACG > GCG | ||
| 987 | G155D | GGC > GAC | GGCCA | |
| 607 | L203M | CTG > ATG | CCCTG | |
| Rat APOBEC1 | 613 | E205K | GAG > AAG | CTCGG |
| 764 | K255T | AAG > ACG | ||
| 987 | Silent | GGG > GGT | TTCCC | |
| 1,245 | silent | AGC > AGT | AGCCG | |
| 758 | R253H | CGC > CAC | TGCGC | |
| 841* | silent | CTG > TTG | AGCTG | |
| 697 | H233D | CAT > GAT | TTCAT | |
| Human APOBEC1 | 699 | H233D | CAT > GAC | |
| 1,149* | Silent | GCC > GCA | GCCAT | |
| 1,245* | F415L | TTT > TTG |
The region analyzed (encompassing exon 13 of BCR and exon 9 of ABL1) includes the imatinib-binding region of the fusion gene. The asterisk indicates mutations found in the same clone. The local sequence context for the mutations at cytosines is shown. Compared to the AID-induced mutations found in previous reports (mutations in approximately 30% of the sequences) [41,42], we found approximately one mutation in each of the clones analyzed. This is explained by the different procedures we used to select resistant clones: whereas the other studies focused on competing bulk populations of AID-transfected GFP(+) cells and control GFP(−) cells, we analyzed individual clones arising from the same number of cells plated in the presence of imatinib.