Background
Methods
Cell lines and cell culture
PRL-3 gene expression and survival analysis
Pooled short-hairpin RNA library screen
Data processing
Small molecule inhibitors
Cell viability assays
Real-time quantitative reverse transcriptase-PCR (qRT-PCR)
Combination index and isobologram analysis
Apoptosis assays
Western blot analysis
Evaluation of combination therapy in leukemia-engrafted mice
Statistical analysis
Results
High expression of PRL-3 is an independent prognostic factor in AML
Genome-wide shRNA synthetic lethal screen against the PRL-3 oncogene
AKT and WNT/β-catenin pathways are key for the survival of AML cells with PRL-3 overexpression
Patient ID | Sex | Age (years) | FAB | Karyotype | FLT3 | NPM1 | PRL-3 status* | Average CI values |
---|---|---|---|---|---|---|---|---|
Pt#1 | M | 44 | M5 | 47,XY,+8 | FLT3-ITD | WT | 35 | 0.29 |
Pt#2 | M | 70 | M4 | Normal | WT | N.A. | 21 | 0.35 |
Pt#3 | F | 34 | M4 | Inv(16)(p13.1q22) | N.A. | N.A. | 23 | 0.33 |
Pt#4 | M | 62 | M3 | add(14)(q24) | FLT3-ITD | Mutant | 19 | 0.47 |
Pt#5 | F | 41 | M2 | Normal | FLT3-ITD | Mutant | 15 | 0.68 |
Pt#6 | F | 37 | M5 | Normal | WT | N.A. | 0.8 | 1.31 |
Pt#7 | M | 33 | M4 | t(3;7)(p25;q22) | N.A. | N.A. | 1.9 | 0.96 |
Pt#8 | F | 75 | M2 | Normal | WT | N.A. | 1.3 | 1.20 |
Pt#9 | M | 26 | M0 | Complex | WT | WT | 0.7 | 1.45 |
Pt#10 | F | 68 | M2 | Normal | WT | Mutant | 1.8 | 0.98 |