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Series GSE182006 Query DataSets for GSE182006
Status Public on Apr 09, 2022
Title Effective therapy of AML with RUNX1 mutation by co-treatment with inhibitors of protein translation and BCL2 [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Majority of RUNX1 mutations in AML are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared to AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1 and c-Myc. Compared to AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. HHT treatment repressed enhancers and their BRD4 occupancy, as well as reduced levels of c-Myc, c-Myb, MCL1 and Bcl-xL. Consistent with this, co-treatment with omacetaxine and venetoclax or BET inhibitor induced synergistic in vitro lethality in AML expressing mtRUNX1. Compared to each agent alone, co-treatment with omacetaxine and venetoclax or BET inhibitor also displayed improved in vivo anti-AML efficacy, associated with improved survival of immune depleted mice engrafted with AML cells harboring mtRUNX1. These findings highlight superior efficacy of omacetaxine-based combination therapies for AML harboring mtRUNX1.
 
Overall design 8 samples
 
Contributor(s) Mill CP, Bhalla KN
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Aug 12, 2021
Last update date Apr 10, 2022
Contact name Yuan Qi
E-mail(s) yqi1@mdanderson.org
Organization name University of Texas M.D. Anderson Cancer Center
Department Bioinformatics & Computational Biology
Street address 1400 Pressler St
City Houston
State/province TX
ZIP/Postal code 77030-4008
Country USA
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (8)
GSM5516049 OCIAML2 Runx1R174*/wt Control ChIP-Input
GSM5516050 OCIAML2 Runx1R174*/wt 100nM HHT ChIP-Input
GSM5516051 OCIAML2 Runx1R174*/wt Control ChIP-H3K27Ac
This SubSeries is part of SuperSeries:
GSE182023 Effective therapy of AML with RUNX1 mutation by co-treatment with inhibitors of protein translation and BCL2
Relations
BioProject PRJNA754174
SRA SRP332304

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
GSE182006_RAW.tar 6.4 Mb (http)(custom) TAR (of BROADPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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