Pair Name |
Homoharringtonine, ACC010 |
Partner Name |
Homoharringtonine |
Disease Info |
[ICD-11: 2A60.Z] |
Acute myeloid leukemia |
Investigative |
Biological Phenomena |
Induction-->Apoptosis |
Gene Regulation |
Down-regulation |
Phosphorylation |
AKT1
|
hsa207
|
Up-regulation |
Cleavage |
CASP3
|
hsa836
|
Up-regulation |
Cleavage |
CASP7
|
hsa840
|
Down-regulation |
Expression |
CDK2
|
hsa1017
|
Down-regulation |
Expression |
CDK4
|
hsa1019
|
Down-regulation |
Expression |
CDK6
|
hsa1021
|
Up-regulation |
Expression |
CDKN1A
|
hsa1026
|
Down-regulation |
Phosphorylation |
FLT3
|
hsa2322
|
Down-regulation |
Expression |
MYC
|
hsa4609
|
Up-regulation |
Cleavage |
PARP1
|
hsa142
|
Up-regulation |
Expression |
PSMD9
|
hsa5715
|
Down-regulation |
Phosphorylation |
RB1
|
hsa5925
|
Down-regulation |
Phosphorylation |
STAT5
|
hsa6776
|
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. |