Activation of the RAS–to–mitogen-activated protein kinase signaling cascade in myeloid leukemia cell lines
| Cell line . | Leukemia . | RASmutation . | Activation of . | |||
|---|---|---|---|---|---|---|
| RAS . | ERK-1/2 . | MEK-1/2 . | CREB-1/ATF-1 . | |||
| HL-60 | AML M2 | N-RAS/61 | (+) | ++ | ++ | ++ |
| Kasumi-1 | AML M2 | K-RAS/12 | — | (+) | ++ | + |
| Mutz-2 | AML M2 | None | — | (+) | — | + |
| NB-4 t15;17 PML/RARA | AML M3 | None | +++ | +++ | +++ | ++ |
| THP-1 | AML M4 | N-RAS/12 | (+) | ++ | (+) | — |
| PLB-985 | AML M4 | None | — | ++ | — | + |
| OCI-AML2 | AML M4 | None | — | + | + | +++ |
| OCI-AML5 | AML M4 | None | — | (+) | — | — |
| Mutz-3 | AML M4 | None | — | (+) | (+) | — |
| ML-2 t6;11, MLL/AF6 | AML M4 | None | — | + | + | +++ |
| MV4-11 t4;11, MLL/AF4 | AML M5 | K-RAS/12 | — | +++ | (+) | + |
| K-RAS/18 | ||||||
| Mono-Mac-1 | AML M5 | None | — | +++ | ++ | +++ |
| KG-1 | AML M6 | None | — | + | ++ | + |
| M-07e | AML M7 | None | — | (+) | + | ++ |
| RC2A | ALL | None | — | + | + | + |
| EM-2 | CML blast crisis | BCR-Abl | — | — | + | + |
| JK-1 | CML erythroid blast crisis | BCR-Abl | — | — | + | |
| K562 | CML blast crisis | BCR-Abl | — | + | + | ++ |
| MEG-01 | CML megakaryocytic blast crisis | BCR-Abl | — | + | + | + |
| LAMA-84 | CML myeloid-megakaryocytic blast crisis | BCR-Abl | — | — | +++ | |
| Cell line . | Leukemia . | RASmutation . | Activation of . | |||
|---|---|---|---|---|---|---|
| RAS . | ERK-1/2 . | MEK-1/2 . | CREB-1/ATF-1 . | |||
| HL-60 | AML M2 | N-RAS/61 | (+) | ++ | ++ | ++ |
| Kasumi-1 | AML M2 | K-RAS/12 | — | (+) | ++ | + |
| Mutz-2 | AML M2 | None | — | (+) | — | + |
| NB-4 t15;17 PML/RARA | AML M3 | None | +++ | +++ | +++ | ++ |
| THP-1 | AML M4 | N-RAS/12 | (+) | ++ | (+) | — |
| PLB-985 | AML M4 | None | — | ++ | — | + |
| OCI-AML2 | AML M4 | None | — | + | + | +++ |
| OCI-AML5 | AML M4 | None | — | (+) | — | — |
| Mutz-3 | AML M4 | None | — | (+) | (+) | — |
| ML-2 t6;11, MLL/AF6 | AML M4 | None | — | + | + | +++ |
| MV4-11 t4;11, MLL/AF4 | AML M5 | K-RAS/12 | — | +++ | (+) | + |
| K-RAS/18 | ||||||
| Mono-Mac-1 | AML M5 | None | — | +++ | ++ | +++ |
| KG-1 | AML M6 | None | — | + | ++ | + |
| M-07e | AML M7 | None | — | (+) | + | ++ |
| RC2A | ALL | None | — | + | + | + |
| EM-2 | CML blast crisis | BCR-Abl | — | — | + | + |
| JK-1 | CML erythroid blast crisis | BCR-Abl | — | — | + | |
| K562 | CML blast crisis | BCR-Abl | — | + | + | ++ |
| MEG-01 | CML megakaryocytic blast crisis | BCR-Abl | — | + | + | + |
| LAMA-84 | CML myeloid-megakaryocytic blast crisis | BCR-Abl | — | — | +++ | |
Among the myeloid leukemia cell lines used in this study are 14 AML cell lines and 5 CML cell lines (all from blast crisis). HL-60 and THP-1 harbor N-RAS mutations in codons 61 and 12 (CAA → CTA and GGT → GAT resulting in Q61L and G12D, respectively). Kasumi-1 and MV4-11 contain a codon 12 K-RAS mutation (GGT → GAT resulting in G12D). An additional codon 18 mutation was detected in MV4-11 (GCC → GAC resulting in A18D). A previously unknown silent H-RAS mutation in codon 59 (GCC → GCT) was observed in MV4-11, Kasumi-1, and NB-4 (Ala). All cell lines were obtained from the German Collection of Microorganisms and Cell Cultures.
AML indicates acute myeloid leukemia; CML, chronic myeloid leukemia.