Table 1.
The gene essentiality analysis performed in silico resulted in the identification of potential metabolic vulnerabilities for the AML THP-1 parental untreated, AraC-resistant and DOX-resistant cell models. The table presents the potential gene targets grouped according to their metabolic pathway. Genes were considered essential for growth, if their KO reduced the flux through biomass reaction to less than 20% of the wild type. The asterisk (*) denotes the essential genes that were identified only upon the integration of the targeted metabolomics dataset.
| Pathway | Targets | Parental | AraC | DOX |
|---|---|---|---|---|
| Pentose phosphate pathway | G6PD, PGD, PGLS | Essential | Essential | Non-essential |
| RPIA | Essential | Essential | Essential | |
| Cholesterol metabolism | CYP51A1, DHCR7, EBP, SQLS, LSS, MSMO1, NSDHL, SQLE, TM7SF2, HSD17B4, HMGCR, MVD, MVK, PMVK | Non-essential | Essential* | Essential* |
| LIPA | Essential | Essential | Essential | |
| Glycolysis | GPI | Essential | Essential | Essential |
| Folate metabolism | ATIC, DHFR, GART, TYMS | Essential | Essential | Essential |
| Sphingolipid metabolism | KDSR, SGMS1, SPTLC1, SPTLC2, SPTLC3 | Essential | Essential | Essential |
| Nucleotide metabolism | ADSL, CAD, CMPK1, DHODH, PAICS, PFAS, PPAT, TXNRD1, UMPS | Essential | Essential | Essential |
| PNP | Essential | Non-essential | Non-essential | |
| Glycerophospholipid metabolism | CRLS1, LCAT, PGS1, PTPMT1 | Essential | Essential | Essential |
| Alanine, aspartate and glutamate metabolism | ASNS | Essential | Essential | Essential |