Inhibition of colony formation and cell viability of myeloid leukemia cell lines by farnesyltransferase inhibitors
| Cell line . | Leukemia . | Ras-to-MAPK . | B581 . | Cys-4 Abs-Met . | FPT2 . | FPT3 . | FTI277 . | FTI276 . |
|---|---|---|---|---|---|---|---|---|
| HL-60 N-RAS/61 | AML M2 | ++ | 14.3 ± 6.2 | 13.1 ± 14.4 | 52.9 ± 2.1 | 84.8 | 100 | 27.1 ± 8.5 |
| Kasumi-1 K-RAS/12 | AML M2 | + | 0 | nd | 90.9 ± 1.0 | 79.1 | 100 | 37.6 ± 7.0 |
| Mutz-2 | AML M2 | (+) | 0 | nd | 0 | 0 | 83.4 ± 1.5 | 15.6 ± 2.5 |
| NB-4 t15;17 PML/RARA | AML M3 | +++ | 0 | 15.5 ± 12.4 | 97.2 ± 1.1 | 100 | 100 | 0 |
| THP-1 N-RAS/12 | AML M4 | ++ | 0 | 0 | 0 | 100 | 87.5 | 25 |
| PBL-985 | AML M4 | + | 0 | 0 | 0 | 32.3 ± 11.2 | 100 | 0 |
| OCI-AML2 | AML M4 | — | 0 | 0 | 0 | 92.1 ± 0.7 | 100 | 46.2 ± 26.4 |
| OCI-AML5 | AML M4 | — | 22.1 ± 6.9 | 39.3 ± 9.2 | 37.3 ± 6.2 | 72.8 ± 4.5 | 100 | 32.1 ± 4.3 |
| Mutz-3 | AML M4 | — | 0 | nd | 15.1 ± 1.3 | 43.2 ± 4.5 | 99.1 ± 0.2 | 0 |
| ML-2 t6;11, MLL/AF6 | AML M4 | + | 0 | 0 | 0 | 0 | 100 | 0 |
| MV4-11 K-RAS/12&18 t4;11, MLL/AF4 | AML M5 | ++ | 25.6 ± 3.0 | 15.5 ± 8.6 | 19.4 ± 10.9 | 52.8 ± 11.3 | 99.8 ± 0.4 | 20.5 ± 8.9 |
| Mono-Mac-1 | AML M5 | +++ | 0 | 70 | 30 | 70 | 80 | 20 |
| KG-1 | AML M6 | + | 0 | 0 | 0 | 0 | 87.5 | 0 |
| M-07e | AML M7 | + | 0 | 0 | 0 | 0 | 96.4 ± 0.9 | 0 |
| EM-2 BCR-Abl | CML | — | 0 | nd | 80.5 ± 1.2 | 100 | 100 | 75.4 ± 6.3 |
| JK-1 BCR-Abl | CML | — | 15.0 ± 2.3 | nd | 16.3 ± 10.1 | 100 | 100 | 0 |
| K562 BCR-Abl | CML | + | 0 | 0 | 0 | 12.6 ± 13.5 | 100 | 0 |
| MEG-01 BCR-Abl | CML | — | 47.7 ± 6.8 | nd | 77.7 ± 0.6 | 79.8 ± 3.2 | 71.6 ± 3.8 | 76.8 ± 4.8 |
| LAMA-84 BCR-Abl | CML | — | 0 | nd | 17.4 ± 10.8 | 40.5 ± 3.0 | 100 | 86.4 ± 3.6 |
| Cell line . | Leukemia . | Ras-to-MAPK . | B581 . | Cys-4 Abs-Met . | FPT2 . | FPT3 . | FTI277 . | FTI276 . |
|---|---|---|---|---|---|---|---|---|
| HL-60 N-RAS/61 | AML M2 | ++ | 14.3 ± 6.2 | 13.1 ± 14.4 | 52.9 ± 2.1 | 84.8 | 100 | 27.1 ± 8.5 |
| Kasumi-1 K-RAS/12 | AML M2 | + | 0 | nd | 90.9 ± 1.0 | 79.1 | 100 | 37.6 ± 7.0 |
| Mutz-2 | AML M2 | (+) | 0 | nd | 0 | 0 | 83.4 ± 1.5 | 15.6 ± 2.5 |
| NB-4 t15;17 PML/RARA | AML M3 | +++ | 0 | 15.5 ± 12.4 | 97.2 ± 1.1 | 100 | 100 | 0 |
| THP-1 N-RAS/12 | AML M4 | ++ | 0 | 0 | 0 | 100 | 87.5 | 25 |
| PBL-985 | AML M4 | + | 0 | 0 | 0 | 32.3 ± 11.2 | 100 | 0 |
| OCI-AML2 | AML M4 | — | 0 | 0 | 0 | 92.1 ± 0.7 | 100 | 46.2 ± 26.4 |
| OCI-AML5 | AML M4 | — | 22.1 ± 6.9 | 39.3 ± 9.2 | 37.3 ± 6.2 | 72.8 ± 4.5 | 100 | 32.1 ± 4.3 |
| Mutz-3 | AML M4 | — | 0 | nd | 15.1 ± 1.3 | 43.2 ± 4.5 | 99.1 ± 0.2 | 0 |
| ML-2 t6;11, MLL/AF6 | AML M4 | + | 0 | 0 | 0 | 0 | 100 | 0 |
| MV4-11 K-RAS/12&18 t4;11, MLL/AF4 | AML M5 | ++ | 25.6 ± 3.0 | 15.5 ± 8.6 | 19.4 ± 10.9 | 52.8 ± 11.3 | 99.8 ± 0.4 | 20.5 ± 8.9 |
| Mono-Mac-1 | AML M5 | +++ | 0 | 70 | 30 | 70 | 80 | 20 |
| KG-1 | AML M6 | + | 0 | 0 | 0 | 0 | 87.5 | 0 |
| M-07e | AML M7 | + | 0 | 0 | 0 | 0 | 96.4 ± 0.9 | 0 |
| EM-2 BCR-Abl | CML | — | 0 | nd | 80.5 ± 1.2 | 100 | 100 | 75.4 ± 6.3 |
| JK-1 BCR-Abl | CML | — | 15.0 ± 2.3 | nd | 16.3 ± 10.1 | 100 | 100 | 0 |
| K562 BCR-Abl | CML | + | 0 | 0 | 0 | 12.6 ± 13.5 | 100 | 0 |
| MEG-01 BCR-Abl | CML | — | 47.7 ± 6.8 | nd | 77.7 ± 0.6 | 79.8 ± 3.2 | 71.6 ± 3.8 | 76.8 ± 4.8 |
| LAMA-84 BCR-Abl | CML | — | 0 | nd | 17.4 ± 10.8 | 40.5 ± 3.0 | 100 | 86.4 ± 3.6 |
Cells were seeded at 1.0-2.5 × 105/mL of cell suspension in a 96-well plate and treated with 50 μM inhibitor or solvent control for 4 days. Aliquots of the cell suspensions were then plated in 400 μL methylcellulose for 7 to 14 days and cell growth was evaluated as described in “Materials and methods.” Inhibition is given in percentage of solvent control.
MAPK indicates mitogen-activated protein kinase; nd, not determined; for other abbreviations see Table 1.