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| Status |
Public on Apr 07, 2021 |
| Title |
Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: To show that 8-Cl-Ado can target FAO and synergizes with VEN to significantly decrease the oxygen consumption rate (OCR) and in turn OXPHOS in CD34-enriched AML cells.
Methods: Using AML cell lines and LSC-enriched blast cells from pre-treatment AML patients, we evaluated the effects of 8-Cl-Ado, VEN and the 8-Cl-Ado/VEN combination on fatty acid metabolism, glycolysis and OXPHOS using liquid scintillation counting, a Seahorse XF Analyzer and gene set enrichment analysis (GSEA).
Results: We here report that VEN and 8-Cl-Ado synergistically inhibited in vitro growth of AML cells. Furthermore, immunodeficient mice engrafted with MV4-11-Luc AML cells and treated with the combination of VEN plus 8-Cl-Ado had a significantly longer survival than mice treated with either drugs alone (p≤0.006).
Conclusion: Taken together, the results suggest that 8-Cl-Ado enhances the antileukemic activity of VEN and that this combination represents a promising therapeutic regimen for treatment of AML.
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| Overall design |
We treated MV4-11 AML cells with 250 nM 8-chloro-adenosine, 10 nM venetoclax, combination of both or control, for 4h, 12 h and 24h, all in duplicates. combination of both or control, for 12 h and 24h, all in duplicates.
We also treated KG-1a AML cells with 500 nM 8-chloro-adenosine, 10 nM venetoclax, combination of both or control, for 12 h and 24h, all in duplicates.
Finally, we treated primary AML blasts from 2 different patients (14269-HTB19-005, and 14269-HTB20-006) with 500 nM 8-chloro-adenosine, 10 nM venetoclax, combination of both or control, for 24h
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/33902674/
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| Contributor(s) |
Buettner R, Rosen S, Xuan L, Nguyen T, Sanchez J, Marcucci G, Wu X, Chen M |
| Citation(s) |
33902674 |
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| Submission date |
Apr 06, 2021 |
| Last update date |
Feb 26, 2024 |
| Contact name |
Le Xuan Truong Nguyen |
| Organization name |
City of Hope
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| Department |
Hematology/Bone Marrow T MC
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| Street address |
1218 S 5TH AVE
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| City |
Monrovia |
| State/province |
CA |
| ZIP/Postal code |
91016 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA720054 |
| SRA |
SRP313650 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE171552_read_counts_HTB+KG1A.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE171552_read_counts_MV411.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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