Genes associated with DNA repair pathways are down-regulated in AML1-ETO–expressing cells
| Entrez Gene ID . | Gene symbol . | Gene name . | Affymetrix fold change* . | RQ-PCR† . | AML patient database‡ . | ||
|---|---|---|---|---|---|---|---|
| Week 1 . | Week 5 . | Fold change t(8;21)/non-t(8;21) . | P . | ||||
| Base excision repair | |||||||
| 5426 | POLE | Polymerase (DNA directed), epsilon | −6.10 | −1.3 | −1.5 | 1.1 | — |
| 4968 | OGG1 | 8-oxoguanine DNA glycosylase | −3.70 | −1.8 | −1.8 | −1.7 | <.001 |
| 11277 | TREX1 | Three prime repair exonuclease 1 | −3.52 | −1.7 | −2.6 | −1.2 | <.001 |
| 8930 | MBD4 | Methyl-CpG–binding domain protein 4 | −3.18 | NC | −1.9 | 1.0 | |
| 7374 | UNG | Uracil-DNA glycosylase | −2.33 | NC | NC | 1.0 | — |
| 23583 | SMUG1 | Uracil-DNA glycosylase 1 | — | — | — | — | — |
| Monofunctional single-strand selective | NC | −2.0 | −2.4 | 1.0 | — | ||
| 4350 | MPG | Methylpurine-DNA glycosylase | (−2.08) | −1.7 | −2.5 | −1.4 | <.001 |
| 2237 | FEN1 | Flap structure–specific glycosylase 1 | (−1.79) | −1.9 | −2.6 | −1.5 | <.001 |
| 5591 | PRKDC | Protein kinase, DNA-activated (DNA-PK) | −2.06 | NC | NC | −1.2 | <.05 |
| 3978 | LIG1 | DNA ligase I | −1.79 | (−1.4) | (−1.6) | −1.3 | <.001 |
| Fanconi anemia group | |||||||
| 2175 | FANCA | Fanconi anemia, complementation group A | −3.175 | −1.7 | −1.9 | 1.1 | — |
| 55120 | FANCL | Fanconi anemia, complementation group L | −2.604 | — | — | 1.0 | — |
| 675 | BRCA2 | Breast cancer 2, early onset (=FANCD1) | −2.525 | — | — | 1.0 | — |
| 2188 | FANCF | Fanconi anemia, complementation group F | −1.880 | — | — | 1.1 | — |
| Miscellaneous DNA repair | |||||||
| 472 | ATM | Ataxia telangiectasia mutated | −3.937 | −1.6 | −1.2 | 1.1 | — |
| 993 | CDC25A | Cell division cycle 25A | −2.809 | — | — | 1.0 | — |
| 5884 | RAD17 | RAD17 homolog (S pombe) | −2.674 | −1.4 | −1.6 | NA | — |
| 5580 | PRKCD | Protein kinase C, delta | −2.488 | — | — | −2.9 | <.001 |
| 10111 | RAD50 | RAD50 homolog (S cerevisiae) | −2.381 | — | — | 1.1 | — |
| Entrez Gene ID . | Gene symbol . | Gene name . | Affymetrix fold change* . | RQ-PCR† . | AML patient database‡ . | ||
|---|---|---|---|---|---|---|---|
| Week 1 . | Week 5 . | Fold change t(8;21)/non-t(8;21) . | P . | ||||
| Base excision repair | |||||||
| 5426 | POLE | Polymerase (DNA directed), epsilon | −6.10 | −1.3 | −1.5 | 1.1 | — |
| 4968 | OGG1 | 8-oxoguanine DNA glycosylase | −3.70 | −1.8 | −1.8 | −1.7 | <.001 |
| 11277 | TREX1 | Three prime repair exonuclease 1 | −3.52 | −1.7 | −2.6 | −1.2 | <.001 |
| 8930 | MBD4 | Methyl-CpG–binding domain protein 4 | −3.18 | NC | −1.9 | 1.0 | |
| 7374 | UNG | Uracil-DNA glycosylase | −2.33 | NC | NC | 1.0 | — |
| 23583 | SMUG1 | Uracil-DNA glycosylase 1 | — | — | — | — | — |
| Monofunctional single-strand selective | NC | −2.0 | −2.4 | 1.0 | — | ||
| 4350 | MPG | Methylpurine-DNA glycosylase | (−2.08) | −1.7 | −2.5 | −1.4 | <.001 |
| 2237 | FEN1 | Flap structure–specific glycosylase 1 | (−1.79) | −1.9 | −2.6 | −1.5 | <.001 |
| 5591 | PRKDC | Protein kinase, DNA-activated (DNA-PK) | −2.06 | NC | NC | −1.2 | <.05 |
| 3978 | LIG1 | DNA ligase I | −1.79 | (−1.4) | (−1.6) | −1.3 | <.001 |
| Fanconi anemia group | |||||||
| 2175 | FANCA | Fanconi anemia, complementation group A | −3.175 | −1.7 | −1.9 | 1.1 | — |
| 55120 | FANCL | Fanconi anemia, complementation group L | −2.604 | — | — | 1.0 | — |
| 675 | BRCA2 | Breast cancer 2, early onset (=FANCD1) | −2.525 | — | — | 1.0 | — |
| 2188 | FANCF | Fanconi anemia, complementation group F | −1.880 | — | — | 1.1 | — |
| Miscellaneous DNA repair | |||||||
| 472 | ATM | Ataxia telangiectasia mutated | −3.937 | −1.6 | −1.2 | 1.1 | — |
| 993 | CDC25A | Cell division cycle 25A | −2.809 | — | — | 1.0 | — |
| 5884 | RAD17 | RAD17 homolog (S pombe) | −2.674 | −1.4 | −1.6 | NA | — |
| 5580 | PRKCD | Protein kinase C, delta | −2.488 | — | — | −2.9 | <.001 |
| 10111 | RAD50 | RAD50 homolog (S cerevisiae) | −2.381 | — | — | 1.1 | — |
NC indicates gene expression is not significantly changed between the 2 groups (Welch t test at cutoff level P < .05); NA, probe set not present on chip; and —, not applicable.
Fold change in expression between AML1-ETO and control samples, detected using the Affymetrix U133 Plus 2 gene chip. Numbers in parentheses did not reach statistical significance.
RQ-PCR confirmation on independent samples (purified AML1-ETO cells compared with control transduced cells at indicated times after transduction; data are representative values from 2 separate experiments).
Published Affymetrix data from AML patient samples (Ross et al38 ) for the same genes. Significance levels were determined using a Welch 2-sided t test with Benjamini-Hochberg multiple testing correction. For the non-t(8;21) samples, the T-cell acute lymphoblastic leukemia (T-ALL), adult, and inv(16) groups have been excluded from the comparison.