In vivo effects of flavopiridol on gene blast cell gene expression from 12 AML patients treated at dose level 5 (30 mg/m2 bolus, 60 mg/m2 infusion)
| . | HMGA1 . | STAT3 . | E2F1 . | POLR2A . | VEGFA . | MCL1 . | CyclinD1 . | BCL2 . |
|---|---|---|---|---|---|---|---|---|
| All (12) | ||||||||
| Median* | 0.65 | 0.7 | 0.5 | 0.75 | 0.4 | 1.14 | 6.0 | 7.5 |
| Range | 0.2-1.15 | 0.1-1.4 | 0.1-1.0 | 0.2-1.9 | 0.07-6.1 | 0.2-4.9 | 0.9-11.8 | 3.9-80 |
| Decrease† | 10 (83%) | 8 (67%) | 9 (75%) | 8 (67%) | 8 (67%) | 2 (17%) | 0 | 0 |
| Increase‡ | 0 | 1 (8%) | 0 | 1 (8%) | 4 (33%) | 5 (42%) | 10 (83%) | 12 (100%) |
| P < .05§ | 9 (75%) | 9 (75%) | 9 (75%) | 9 (75%) | 9 (75%) | 7 (58%) | 9 (75%) | 12 (100%) |
| CR (8) | ||||||||
| Median | 0.6 | 0.7 | 0.5 | 0.8 | 0.3 | 1.1 | 6.0 | 7.1 |
| Range | 0.2-1.15 | 0.3-1.0 | 0.1-1.0 | 0.1-1.9 | 0.07-2.5 | 0.2-4.9 | 0.9-11.6 | 3.9-11.7 |
| Decrease | 7 (88%) | 6 (75%) | 6 (75%) | 4 (50%) | 7 (88%) | 2 (25%) | 0 | 0 |
| Increase | 0 | 0 | 0 | 1 (13%) | 1 (13%) | 3 (38%) | 6 (75%) | 8 (100%) |
| P < .05 | 6 (75%) | 6 (75%) | 6 (75%) | 5 (63%) | 7 (88%) | 5 (63%) | 5 (63%) | 8 (100%) |
| NR (4) | ||||||||
| Median | 0.6 | 0.6 | 0.5 | 0.3 | 1.5 | 1.2 | 6.5 | 9.5 |
| Range | 0.5-0.7 | 0.1-1.4 | 0.4-1.0 | 0.2-0.5 | 0.14-6.1 | 1.0-1.7 | 2.1-11.8 | 7.4-80 |
| Decrease | 4 (100%) | 3 (75%) | 3 (75%) | 4 (100%) | 1 (25%) | 0 | 0 | 0 |
| Increase | 0 | 1 (25%) | 0 | 0 | 3 (75%) | 3 (75%) | 4 (100%) | 4 (100%) |
| P < .05 | 3 (75%) | 3 (75%) | 3 (75%) | 4 (100%) | 2 (50%) | 2 (50%) | 4 (100%) | 4 (100%) |
| . | HMGA1 . | STAT3 . | E2F1 . | POLR2A . | VEGFA . | MCL1 . | CyclinD1 . | BCL2 . |
|---|---|---|---|---|---|---|---|---|
| All (12) | ||||||||
| Median* | 0.65 | 0.7 | 0.5 | 0.75 | 0.4 | 1.14 | 6.0 | 7.5 |
| Range | 0.2-1.15 | 0.1-1.4 | 0.1-1.0 | 0.2-1.9 | 0.07-6.1 | 0.2-4.9 | 0.9-11.8 | 3.9-80 |
| Decrease† | 10 (83%) | 8 (67%) | 9 (75%) | 8 (67%) | 8 (67%) | 2 (17%) | 0 | 0 |
| Increase‡ | 0 | 1 (8%) | 0 | 1 (8%) | 4 (33%) | 5 (42%) | 10 (83%) | 12 (100%) |
| P < .05§ | 9 (75%) | 9 (75%) | 9 (75%) | 9 (75%) | 9 (75%) | 7 (58%) | 9 (75%) | 12 (100%) |
| CR (8) | ||||||||
| Median | 0.6 | 0.7 | 0.5 | 0.8 | 0.3 | 1.1 | 6.0 | 7.1 |
| Range | 0.2-1.15 | 0.3-1.0 | 0.1-1.0 | 0.1-1.9 | 0.07-2.5 | 0.2-4.9 | 0.9-11.6 | 3.9-11.7 |
| Decrease | 7 (88%) | 6 (75%) | 6 (75%) | 4 (50%) | 7 (88%) | 2 (25%) | 0 | 0 |
| Increase | 0 | 0 | 0 | 1 (13%) | 1 (13%) | 3 (38%) | 6 (75%) | 8 (100%) |
| P < .05 | 6 (75%) | 6 (75%) | 6 (75%) | 5 (63%) | 7 (88%) | 5 (63%) | 5 (63%) | 8 (100%) |
| NR (4) | ||||||||
| Median | 0.6 | 0.6 | 0.5 | 0.3 | 1.5 | 1.2 | 6.5 | 9.5 |
| Range | 0.5-0.7 | 0.1-1.4 | 0.4-1.0 | 0.2-0.5 | 0.14-6.1 | 1.0-1.7 | 2.1-11.8 | 7.4-80 |
| Decrease | 4 (100%) | 3 (75%) | 3 (75%) | 4 (100%) | 1 (25%) | 0 | 0 | 0 |
| Increase | 0 | 1 (25%) | 0 | 0 | 3 (75%) | 3 (75%) | 4 (100%) | 4 (100%) |
| P < .05 | 3 (75%) | 3 (75%) | 3 (75%) | 4 (100%) | 2 (50%) | 2 (50%) | 4 (100%) | 4 (100%) |
Fold change in mRNA expression in blasts obtained 2 hours after the end of the flavopiridol infusion relative to mRNA expression in pretreatment blasts.
No. (%) of patients' blast cell populations in which flavopiridol was associated with a 20% or greater decrease in target gene mRNA.
No. (%) of patients' blast cell populations in which flavopiridol was associated with a 20% or greater increase in target gene mRNA.
Two-tailed t test, signifying the number (percentage) of patients whose blasts evinced significant (P < .05) increase or decrease in mRNA expression for each gene tested.