Comparative expression profiling defined candidate genes for GC-induced apoptosis
. | . | Childhood ALL . | . | . | . | . | Additional systems . | . | . | . | . | . | . | . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | Frequency in children† . | . | . | . | . | . | In vitro response|| . | . | . | . | Mouse¶ . | . | |||||||||||
| Symbol . | Description . | Mean ± SD* . | PA . | 6 h . | 24 h . | Opp . | Adult‡ . | HD§ . | Sens . | Res . | Conv . | CHX# . | In vivo . | In vitro . | |||||||||||
| PFKFB2 | PFK2.2 | 1.6±0.6 | 11 | 9 | 10 | 0 | Y | 0 | 2 | 1 | 2 | Y | N | N | |||||||||||
| BTNL9 | Butyrophilin-like 9 | 1.6±0.7 | 11 | 9 | 8 | 0 | N | 0 | 2 | 1 | 1 | NA | N | N | |||||||||||
| SNFILK | SNF1-like kinase | 1.7±0.9 | 11 | 5 | 10 | 2 | Y | 0 | 2 | 1 | NA | NA | Y | N | |||||||||||
| FKBP5 | FK506 binding protein 51 | 1.8±0.6 | 10 | 7 | 9 | 0 | Y | 2 | 3 | 3 | 2 | Y | Y | Y | |||||||||||
| ZBTB16? | ZFand BTB domain 16? | 2.6±1.6 | 10 | 7 | 8 | 0 | Y | 2 | 2 | 1 | 2 | NA | N | N | |||||||||||
| KIF26A | Kinesin family member 26A | 1.6±0.3 | 10 | 7 | 6 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| SLA | Src-like-adaptor | 1.7±0.5 | 9 | 7 | 9 | 0 | Y | 0 | 3 | 2 | Y/N | N | N | N | |||||||||||
| SOCS1 | SOCS-1 | 2.5±1.0 | 9 | 6 | 8 | 0 | Y | 2 | 2 | 1 | Y/N | N | Opp | Opp | |||||||||||
| DDIT4 | DNA-damage-ind.transcript 4 | 1.9±0.7 | 9 | 6 | 8 | 0 | Y | 2 | 3 | 2 | 2 | Y | Y | Y | |||||||||||
| GBP4 | Guanylate binding protein 4 | –1.4±0.2 | 9 | 5 | 8 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| MGC17330 | HGFL gene | 1.3±0.3 | 9 | 5 | 9 | 0 | Y | 1 | 3 | 1 | 2 | Y | Y | Y | |||||||||||
| ZFP36L2 | Zinc finger protein 36 | 1.4±0.5 | 8 | 5 | 7 | 0 | Y | 0 | 3 | 2 | Y/N | Y | Y | Y | |||||||||||
| Unknown | Unknown | 1.5±0.3 | 8 | 5 | 8 | 0 | N | 0 | 2 | 0 | 2 | NA | NA | NA | |||||||||||
| EPPK1 | Epiplakin 1 | 1.9±0.6 | 7 | 7 | 6 | 0 | N | 0 | 1 | 0 | NA | NA | Y | N | |||||||||||
| P2RY14 | Purinergic receptor P2Y | 1.7±0.7 | 7 | 5 | 6 | 0 | N | 0 | 2 | 1 | 0 | NA | Y | Y | |||||||||||
| FGR | Gardner-Rasheed v-fgr | 1.5±0.3 | 7 | 5 | 4 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| WFS1 | Wolframin | 1.7±0.3 | 7 | 5 | 6 | 0 | N | 0 | 3 | 1 | Y/N | N | N | N | |||||||||||
| ARPP-21 | cAMP-regulated PP21 | –1.6±0.7 | 7 | 5 | 3 | 0 | N | 0 | 0 | 0 | NA | NA | N | Y | |||||||||||
| SERPINA1 | Proteinase inhibitor, clade A | 1.8±0.5 | 7 | 6 | 4 | 3 | N | 0 | 0 | 0 | NA | NA | N | Opp | |||||||||||
| GIMAP7 | GTPase, IMAP family M7 | –1.3±0.3 | 7 | 6 | 3 | 3 | Y | 0 | 0 | 1 | NA | NA | N | N | |||||||||||
| MYCPBP | c-myc promoter BP | 1.7±0.1 | 7 | 5 | 3 | 2 | N | 0 | 0 | 0 | NA | NA | N | N | |||||||||||
| LGALS3 | Galectin 3 | 1.3±0.4 | 7 | 5 | 3 | 1 | N | 0 | 0 | 0 | NA | NA | N | N | |||||||||||
. | . | Childhood ALL . | . | . | . | . | Additional systems . | . | . | . | . | . | . | . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | Frequency in children† . | . | . | . | . | . | In vitro response|| . | . | . | . | Mouse¶ . | . | |||||||||||
| Symbol . | Description . | Mean ± SD* . | PA . | 6 h . | 24 h . | Opp . | Adult‡ . | HD§ . | Sens . | Res . | Conv . | CHX# . | In vivo . | In vitro . | |||||||||||
| PFKFB2 | PFK2.2 | 1.6±0.6 | 11 | 9 | 10 | 0 | Y | 0 | 2 | 1 | 2 | Y | N | N | |||||||||||
| BTNL9 | Butyrophilin-like 9 | 1.6±0.7 | 11 | 9 | 8 | 0 | N | 0 | 2 | 1 | 1 | NA | N | N | |||||||||||
| SNFILK | SNF1-like kinase | 1.7±0.9 | 11 | 5 | 10 | 2 | Y | 0 | 2 | 1 | NA | NA | Y | N | |||||||||||
| FKBP5 | FK506 binding protein 51 | 1.8±0.6 | 10 | 7 | 9 | 0 | Y | 2 | 3 | 3 | 2 | Y | Y | Y | |||||||||||
| ZBTB16? | ZFand BTB domain 16? | 2.6±1.6 | 10 | 7 | 8 | 0 | Y | 2 | 2 | 1 | 2 | NA | N | N | |||||||||||
| KIF26A | Kinesin family member 26A | 1.6±0.3 | 10 | 7 | 6 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| SLA | Src-like-adaptor | 1.7±0.5 | 9 | 7 | 9 | 0 | Y | 0 | 3 | 2 | Y/N | N | N | N | |||||||||||
| SOCS1 | SOCS-1 | 2.5±1.0 | 9 | 6 | 8 | 0 | Y | 2 | 2 | 1 | Y/N | N | Opp | Opp | |||||||||||
| DDIT4 | DNA-damage-ind.transcript 4 | 1.9±0.7 | 9 | 6 | 8 | 0 | Y | 2 | 3 | 2 | 2 | Y | Y | Y | |||||||||||
| GBP4 | Guanylate binding protein 4 | –1.4±0.2 | 9 | 5 | 8 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| MGC17330 | HGFL gene | 1.3±0.3 | 9 | 5 | 9 | 0 | Y | 1 | 3 | 1 | 2 | Y | Y | Y | |||||||||||
| ZFP36L2 | Zinc finger protein 36 | 1.4±0.5 | 8 | 5 | 7 | 0 | Y | 0 | 3 | 2 | Y/N | Y | Y | Y | |||||||||||
| Unknown | Unknown | 1.5±0.3 | 8 | 5 | 8 | 0 | N | 0 | 2 | 0 | 2 | NA | NA | NA | |||||||||||
| EPPK1 | Epiplakin 1 | 1.9±0.6 | 7 | 7 | 6 | 0 | N | 0 | 1 | 0 | NA | NA | Y | N | |||||||||||
| P2RY14 | Purinergic receptor P2Y | 1.7±0.7 | 7 | 5 | 6 | 0 | N | 0 | 2 | 1 | 0 | NA | Y | Y | |||||||||||
| FGR | Gardner-Rasheed v-fgr | 1.5±0.3 | 7 | 5 | 4 | 0 | N | 0 | 1 | 0 | NA | NA | N | N | |||||||||||
| WFS1 | Wolframin | 1.7±0.3 | 7 | 5 | 6 | 0 | N | 0 | 3 | 1 | Y/N | N | N | N | |||||||||||
| ARPP-21 | cAMP-regulated PP21 | –1.6±0.7 | 7 | 5 | 3 | 0 | N | 0 | 0 | 0 | NA | NA | N | Y | |||||||||||
| SERPINA1 | Proteinase inhibitor, clade A | 1.8±0.5 | 7 | 6 | 4 | 3 | N | 0 | 0 | 0 | NA | NA | N | Opp | |||||||||||
| GIMAP7 | GTPase, IMAP family M7 | –1.3±0.3 | 7 | 6 | 3 | 3 | Y | 0 | 0 | 1 | NA | NA | N | N | |||||||||||
| MYCPBP | c-myc promoter BP | 1.7±0.1 | 7 | 5 | 3 | 2 | N | 0 | 0 | 0 | NA | NA | N | N | |||||||||||
| LGALS3 | Galectin 3 | 1.3±0.4 | 7 | 5 | 3 | 1 | N | 0 | 0 | 0 | NA | NA | N | N | |||||||||||
PA indicates patients analyzed; Opp, number of patients showing regulation in the opposite direction; HD, healthy donor; Sens, GC-sensitive systems; Res, GC-resistant systems; Conv, converted systems; and NA, not applicable.
Mean ± SD of M values from regulated samples after 6 to 8 hours of GC exposure in vivo
Number of patients with M values of 1.0 or higher after 6 hours, 24 hours, and 6 or 24 hours in vivo exposure to GCs (for treatment details see Supplement)
Regulation (Y), or lack thereof (N), in lymphoblasts from an adult patient with ALL treated with GCs in vivo
2, 1, or 0 indicates whether the peripheral blood lymphocytes of both (2), either 1 (1), or none (0) of the 2 healthy volunteers responded with M values of 1.0 or higher after 6-hour and/or 24-hour in vivo exposure to GCs (for treatment details see Supplement)
For each gene, the number of in vitro systems showing M values of 1.0 or higher after 6-hour and/or 24-hour exposure to 10-7 M dexamethasone is indicated. GC-sensitive systems: BCP-ALL-40 (treated ex vivo), CEM-C7H2, PreB-697; GC-resistant systems: CEM-C1, CEM-C7R1, CEM-C7R1dim-low, PreB-697-R4G4; converted systems: CEM-C1ratGR, CEM-C7R1dim-high. If NA, the gene was not regulated in CEM-C7H2 (and hence cannot be “converted”); Y/N indicates regulated in C1ratGR but not in CEM-C7R1dim-high
Y and N indicate whether (Y) or not (N) the respective gene was regulated in CD1 mouse thymocytes after 4-hour exposure to dexamethasone in vivo and/or in vitro, as indicated
Genes regulated (M ≥ 1.0) in CEM-C7H2 cells after 6-hour exposure to 10-7 M dexamethasone in the presence of 10 μg/mL cycloheximide (CHX) are indicated with Y; those no longer regulated in the presence of CHX with N. NA denotes genes that were not regulated by GC in CEM-C7H2 cells in the absence of CHX