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Series GSE171552 Query DataSets for GSE171552
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
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.
 
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
Web link https://pubmed.ncbi.nlm.nih.gov/33902674/
 
Contributor(s) Buettner R, Rosen S, Xuan L, Nguyen T, Sanchez J, Marcucci G, Wu X, Chen M
Citation(s) 33902674
Submission date Apr 06, 2021
Last update date Feb 26, 2024
Contact name WenYong Chen
Organization name City of Hope
Department Department of Cancer Biology and Molecular Medicine
Street address 1500 East Duarte Road
City Duarte
State/province CA
ZIP/Postal code 91010
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (48)
GSM5227033 MV4-11 NT 4H rep1
GSM5227034 MV4-11 NT 4H rep2
GSM5227035 MV4-11 8ClAdo 250nM 4H rep1
Relations
BioProject PRJNA720054
SRA SRP313650

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
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Raw data are available in SRA
Processed data are available on Series record

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