Genetic features and the individual response of the parameters investigated within each CLL sample to establish the miRNA106b-initiated signaling cascade, after exposure to LBH589 or MS275
| Patient no. . | Percentage of cells with del17p (p53)* . | AcH3 . | E2F1 . | MCM7 . | miRNA 106b . | Itch protein . | p73 protein . | PUMA mRNA . | PUMA protein . | Cleaved caspase-9 . | Annexin positivity . | ZAP70 . | p73 mRNA . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 0 | ↑ | —† | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 2 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | — | — | ||
| 3 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 4 | —‖ | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | ↓ | ||
| 5 | 69% | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 6 | 12 double deletion, 9 monosomy‖ | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↑ | ||
| 7 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | — | — |
| 8 | 36 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | not detectable | ↑ | ↑ | — | — |
| 9 | 89 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 10 | 0 | ↑ | — | ↓ | ∼‡ | ∼‡ | not detectable | partial | < 20%§ | negative | ↓ | ||
| 11 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 12 | 18 | ↑ | — | ↓ | ↑ | ↓ | ↑ | ↑ | ↑ | — | ↑ | ||
| 13 | 0 | ↑ | — | ↓ | ∼‡ | ↑ | ↑ | ↑ | ↑ | — | ↓ | ||
| 14 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 15 | 0 | ↑ | — | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | negative | ↓ | ||
| 16 | 67.5 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | ↑ | ||
| 17 | 0 | ↑ | — | ↓ | ↑ | ∼ | ↑ | ↑ | ↑ | — | ↓ | ||
| 18 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ∼ | ||
| 19 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↑ | ||
| 20 | 0 | ↑ | — | ↓ | ∼ | ↓ | ↑ | ↑ | ↑ | — | ↓ | ||
| 21 | 86 | ↑ | + | ↑ | ↑ | ↓ | ∼ | ↓ | ↓ | ↑ | < 20% | positive | ↓ |
| 22 | 9.5 | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ |
| 23 | 70 | ↑ | — | ↓ | ↑ | ↓ | ↓ | ↑ | ↑ | — | ↑ | ||
| 24 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 25 | 82 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | ↓ | ∼ | ↑ | ↑ | — | ↓ |
| 26 | 93 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 27 | 0 | ↑ | + | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | negative | — |
| 28 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | negative | — |
| 29 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ∼ | — | ↑ | ∼ | < 20% | positive | — |
| 30 | 0 | — | — | — | — | — | — | — | — | positive | — | ||
| 31 | 0 | ↑ | — | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | — | ↑ | ||
| 32 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | positive | ↓ |
| 33 | — | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | — |
| 34 | 18 | — | — | — | — | ↑ | — | — | — | positive | — | ||
| 35 | 0 | ↑ | + | ∼ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 36 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 37¶ | 0 | ↑ | — | — | ∼ | ∼ | ∼ | — | — | partial | < 20% | positive | — |
| 38¶ | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 39** | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 40 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | negative | — |
| 41 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 42 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | — | — |
| 43 | 67 | ↑ | + | ↑ | ↑ | positive | |||||||
| 44 | — | neg | ∼ | ∼ | — | ||||||||
| 46 | — | ↑ | + | ∼ | ∼ | — | |||||||
| 47 | — | ↑ | + | ↑ | ↑ | — |
| Patient no. . | Percentage of cells with del17p (p53)* . | AcH3 . | E2F1 . | MCM7 . | miRNA 106b . | Itch protein . | p73 protein . | PUMA mRNA . | PUMA protein . | Cleaved caspase-9 . | Annexin positivity . | ZAP70 . | p73 mRNA . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 0 | ↑ | —† | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 2 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | — | — | ||
| 3 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 4 | —‖ | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | ↓ | ||
| 5 | 69% | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 6 | 12 double deletion, 9 monosomy‖ | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↑ | ||
| 7 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | — | — |
| 8 | 36 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | not detectable | ↑ | ↑ | — | — |
| 9 | 89 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 10 | 0 | ↑ | — | ↓ | ∼‡ | ∼‡ | not detectable | partial | < 20%§ | negative | ↓ | ||
| 11 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 12 | 18 | ↑ | — | ↓ | ↑ | ↓ | ↑ | ↑ | ↑ | — | ↑ | ||
| 13 | 0 | ↑ | — | ↓ | ∼‡ | ↑ | ↑ | ↑ | ↑ | — | ↓ | ||
| 14 | 0 | ↑ | — | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — | ||
| 15 | 0 | ↑ | — | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | negative | ↓ | ||
| 16 | 67.5 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | ↑ | ||
| 17 | 0 | ↑ | — | ↓ | ↑ | ∼ | ↑ | ↑ | ↑ | — | ↓ | ||
| 18 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ∼ | ||
| 19 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↑ | ||
| 20 | 0 | ↑ | — | ↓ | ∼ | ↓ | ↑ | ↑ | ↑ | — | ↓ | ||
| 21 | 86 | ↑ | + | ↑ | ↑ | ↓ | ∼ | ↓ | ↓ | ↑ | < 20% | positive | ↓ |
| 22 | 9.5 | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ |
| 23 | 70 | ↑ | — | ↓ | ↑ | ↓ | ↓ | ↑ | ↑ | — | ↑ | ||
| 24 | 0 | ↑ | — | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | positive | ↓ | ||
| 25 | 82 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | ↓ | ∼ | ↑ | ↑ | — | ↓ |
| 26 | 93 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 27 | 0 | ↑ | + | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | negative | — |
| 28 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | negative | — |
| 29 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ∼ | — | ↑ | ∼ | < 20% | positive | — |
| 30 | 0 | — | — | — | — | — | — | — | — | positive | — | ||
| 31 | 0 | ↑ | — | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | — | ↑ | ||
| 32 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ∼ | ↑ | ↑ | positive | ↓ |
| 33 | — | ↑ | + | ↑ | ↑ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | — | — |
| 34 | 18 | — | — | — | — | ↑ | — | — | — | positive | — | ||
| 35 | 0 | ↑ | + | ∼ | ↑ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 36 | 0 | ↑ | neg | ∼ | ∼ | ↓ | ↑ | — | ↑ | ↑ | ↑ | positive | — |
| 37¶ | 0 | ↑ | — | — | ∼ | ∼ | ∼ | — | — | partial | < 20% | positive | — |
| 38¶ | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 39** | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 40 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | negative | — |
| 41 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | positive | — |
| 42 | 0 | ↑ | + | ↑ | ↑ | ↓ | ↑ | — | — | ↑ | ↑ | — | — |
| 43 | 67 | ↑ | + | ↑ | ↑ | positive | |||||||
| 44 | — | neg | ∼ | ∼ | — | ||||||||
| 46 | — | ↑ | + | ∼ | ∼ | — | |||||||
| 47 | — | ↑ | + | ↑ | ↑ | — |
neg indicates undetectable protein levels.
CLL samples were classified according their p53 FISH status.
No sample.
No change from control.
A total of 20% was used as a cutoff point for determining annexin positivity.
Negative in p21 functional assay.
CLL sample exposed to 3 μM SAHA.
CLL sample exposed to 3 μM MS275.