Table 1. Characterization of ASP3026-resistant cell lines.
Cell proliferation data, qPCR, sequencing analyses and mutant frequency within each population are shown. Frequency is calculated from chromatogram peak height, except in SUPM2R3, where the actual prevalence of TOPO-TA clones is reported (23 clones sequenced; see Methods section).
| Cell line | ASP3026 IC50 [nM] | IC50 fold increase (RR) | NPM/ALK transcript level (normalized) | Mutation (NM_004304.4) | Aminoacid substitution | Frequency (%) |
|---|---|---|---|---|---|---|
| K299 | 19 | 1 | 1 | - | - | |
| K299R1 | 208 | 11 | 3.8 | 4484A > C | N1178H | 100 |
| K299R2 | 552 | 29 | 2.0 | 4463T > C | I1171T | ~50 |
| K299R3 | 550 | 29 | 0.8 | 4484A > C 4418G > A |
N1178H C1156Y |
~40 ~15 |
| SUPM2 | 38 | 1 | 1 | - | - | |
| SUPM2R1 | 1381 | 36 | 2.7 | 4463T > A | I1171N | ~70 |
| SUPM2R2 | 2186 | 58 | 2.4 | 4334/4335 GG > TC | G1128S | 100 |
| SUPM2R3 | 1654 | 44 | 2.5 | 4418G > T/4559G > A 4580G > A 4472T > A 4418G > T other* |
C1156F/D1203N E1210K F1174I C1156F other* |
43 39 9 4 4 |
*
other, refers to a complex deletion within the kinase domain, possibly an artifact of cloning, observed in 1/23 clones.