Overview of response of RA-resistant cells to RA and TNF or HDAC inhibitor
Cell line . | Mutation position/observed change . | Result of mutation . | ATRA activation of RARB . | PML/RAR degraded in response to 72 h of RA? . | Differentiate in response to RA and TNF? . | Differentiate in response to inhibitors of HDAC and RA? . |
|---|---|---|---|---|---|---|
| UF-1 | 276 LBD | Arg-Trp | +/− | — | + | — |
| MRA1 | 410 LBD | Ile-Thr | +/− | +/− | + | + |
| MR4 | 398 LBD | Leu-Pro | — | — | +/− | +/− |
| MR2 | Altered PML/RAR binding profile | — | + | + | + | +/− |
| MR6 | Altered PML/RAR binding profile | — | + | + | + | +/− |
Cell line . | Mutation position/observed change . | Result of mutation . | ATRA activation of RARB . | PML/RAR degraded in response to 72 h of RA? . | Differentiate in response to RA and TNF? . | Differentiate in response to inhibitors of HDAC and RA? . |
|---|---|---|---|---|---|---|
| UF-1 | 276 LBD | Arg-Trp | +/− | — | + | — |
| MRA1 | 410 LBD | Ile-Thr | +/− | +/− | + | + |
| MR4 | 398 LBD | Leu-Pro | — | — | +/− | +/− |
| MR2 | Altered PML/RAR binding profile | — | + | + | + | +/− |
| MR6 | Altered PML/RAR binding profile | — | + | + | + | +/− |
Compilation of data showing genetic lesions in RA-resistant APL cells and their sensitivity to RA and TNF or histone deacetylase (HDAC) inhibitor treatment. Results show that several cell lines resistant to RA and HDAC inhibitors were found to respond well to RA and TNF treatment. Table is based on both new and previously published data.5,35 ATRA indicates all-trans retinoic acid; RARB, retinoic acid receptor β; LBD, ligand-binding domain; +/−, weak response; and—, no response.