Use of additional biological systems for candidate gene evaluation
. | . | Coregulation . | . | |
|---|---|---|---|---|
| Biological system . | Major information . | Yes . | No . | |
| Adult ALL in vivo* | Exclusion of MTX effects; identification of genes coregulated in childhood and adult GC-sensitive ALL | + | – | |
| BCP-ALL-40 ex vivo | Identification of cell autonomous GC effects in primary leukemia cells | + | – | |
| PBL in vivo, GC resistant | Regulated genes do not directly induce cell death | – | + | |
| GC-sensitive ALL cell lines | Coregulation supports cell autonomous effects, GC specificity, and possible role in the death response | + | – | |
| GC-resistant ALL cell lines† | Loss of coregulation compared to sensitive counterpart supports role in death response | – | + | |
| Cell lines with restored GC sensitivity‡ | Restoration of loss of coregulation strongly supports role in death response | + | – | |
| Mouse thymocytes§ | Identification of interspecies conserved response genes | + | – | |
| CHX-treated ALL cell line∥ | Dependence on de novo protein synthesis excludes primary response genes | + | – | |
. | . | Coregulation . | . | |
|---|---|---|---|---|
| Biological system . | Major information . | Yes . | No . | |
| Adult ALL in vivo* | Exclusion of MTX effects; identification of genes coregulated in childhood and adult GC-sensitive ALL | + | – | |
| BCP-ALL-40 ex vivo | Identification of cell autonomous GC effects in primary leukemia cells | + | – | |
| PBL in vivo, GC resistant | Regulated genes do not directly induce cell death | – | + | |
| GC-sensitive ALL cell lines | Coregulation supports cell autonomous effects, GC specificity, and possible role in the death response | + | – | |
| GC-resistant ALL cell lines† | Loss of coregulation compared to sensitive counterpart supports role in death response | – | + | |
| Cell lines with restored GC sensitivity‡ | Restoration of loss of coregulation strongly supports role in death response | + | – | |
| Mouse thymocytes§ | Identification of interspecies conserved response genes | + | – | |
| CHX-treated ALL cell line∥ | Dependence on de novo protein synthesis excludes primary response genes | + | – | |
Whole genome expression profiles were obtained from the systems listed prior to and after exposure to GC in vivo or in vitro, as indicated. Performance of a candidate gene in these systems (ie, absence/presence and/or extent of GC regulation) provides evidence, although not conclusive, regarding its possible role in the death pathway and other relevant information (dependence on de novo protein synthesis, interspecies conservation, etc).
The plus and minus symbols indicate whether the respective regulatory behavior of the gene under investigation argues for (+) or against (–) its possible role in the GC-induced cell death pathway
Only informative if gene is regulated in sensitive parental system (CCRF-CEM)
Only informative if gene is regulated in sensitive, but not resistant, parental system (CCRF-CEM)
Only relevant if death pathway is conserved in mouse thymocytes and childhood ALL
Only informative if gene is regulated in CEM-C7H2 after 6-hour GC treatment