
| Pair Name | Homoharringtonine, ACC010 | |||
| Partner Name | Homoharringtonine | |||
| Disease Info | [ICD-11: 2A60.Z] | Acute myeloid leukemia | Investigative | |
| Biological Phenomena | Induction-->Apoptosis | |||
| Gene Regulation | Up-regulation | Cleavage | PARP1 | hsa142 |
| Up-regulation | Cleavage | CASP3 | hsa836 | |
| Up-regulation | Cleavage | CASP7 | hsa840 | |
| Down-regulation | Phosphorylation | RB1 | hsa5925 | |
| Down-regulation | Expression | CDK2 | hsa1017 | |
| Down-regulation | Expression | CDK4 | hsa1019 | |
| Down-regulation | Expression | CDK6 | hsa1021 | |
| Up-regulation | Expression | CDKN1A | hsa1026 | |
| Up-regulation | Expression | PSMD9 | hsa5715 | |
| Down-regulation | Phosphorylation | FLT3 | hsa2322 | |
| Down-regulation | Phosphorylation | STAT5 | hsa6776 | |
| Down-regulation | Phosphorylation | AKT1 | hsa207 | |
| Down-regulation | Expression | MYC | hsa4609 | |
| In Vitro Model | MV4‐11 | Childhood acute monocytic leukemia | Homo sapiens (Human) | CVCL_0064 |
| MOLM-13 | Adult acute myeloid leukemia | Homo sapiens (Human) | CVCL_2119 | |
| In Vivo Model | MOLM13‐luciferase cells (1×10⁶) were injected into each mouse via the tail vein. After 6 days, cell engraftment was assessed after intraperitoneal injection of luciferin. | |||
| Result | ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD. | |||