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Series GSE253748 Query DataSets for GSE253748
Status Public on May 15, 2024
Title Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary MGA (Max-gene associated) is a dual-specificity transcription factor that negatively regulates MYC-target genes to inhibit proliferation and promote differentiation. Loss-of-function mutations in MGA have been commonly identified in several hematological neoplasms, including acute myeloid leukemia (AML) with RUNX1::RUNX1T1, however, very little is known about the impact of these MGA alterations on normal hematopoiesis or disease progression. We show that representative MGA mutations identified in patient samples abolish protein-protein interactions and transcriptional activity. Using a series of human and mouse model systems, including a newly developed conditional knock-out mouse strain, we demonstrate that loss of MGA results in upregulation of MYC and E2F targets, cell cycle genes, mTOR signaling, and oxidative phosphorylation in normal hematopoietic cells, leading to enhanced proliferation. The loss of MGA induces an open chromatin state at promotors of genes involved in cell cycle and proliferation. RUNX1::RUNX1T1 expression in Mga-deficient murine hematopoietic cells leads to a more aggressive AML with a significantly shortened latency. These data show that MGA regulates multiple pro-proliferative pathways in hematopoietic cells and cooperates with the RUNX1::RUNX1T1 fusion oncoprotein to enhance leukemogenesis.
 
Overall design RNA-seq analysis of human (Molm13) or mouse (HSCs) with deletions of MGA
 
Contributor(s) Thomas III ME, Klco JM
Citation(s) 38454121
Submission date Jan 19, 2024
Last update date May 15, 2024
Contact name Michael Walsh
E-mail(s) Michaelp.walsh@stjude.org
Organization name St Jude Children's Research Hospital
Street address 262 Danny Thomas
City Memphis
ZIP/Postal code 38103
Country USA
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (29)
GSM8027359 RNA-seq of Molm13 cells with homozygous deletion of MGA using CRISPR C2
GSM8027360 RNA-seq of Molm13 cells with homozygous deletion of MGA using CRISPR C3
GSM8027361 RNA-seq of Molm13 cells with homozygous deletion of MGA using CRISPR C4
This SubSeries is part of SuperSeries:
GSE253753 Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia
Relations
BioProject PRJNA1066867

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE253748_SJ_MGA_human_RSEM_gene_count_final.txt.gz 833.8 Kb (ftp)(http) TXT
GSE253748_SJ_MGA_mouse_RSEM_gene_count_final.txt.gz 1.6 Mb (ftp)(http) TXT
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