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Series GSE151821 Query DataSets for GSE151821
Status Public on Jun 05, 2020
Title RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [KARPAS-45 AI-10-104 RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with a high incidence of relapse. Here we show that Runt-related transcription factor 2, RUNX2 is upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or immature phenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, while it reciprocally binds the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 is required for survival in immature and KMT2A-R T-ALL in vitro and in vivo. We report a direct transcriptional regulation of CXCR4 signaling by RUNX2, which thereby promotes cell migration and adhesion. Functionally, RUNX2 impacts T-ALL cell homing and exacerbates T-ALL progression to medullary and extramedullary sites. We demonstrate that RUNX2 enables these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation results in increased mitochondrial dynamics and biogenesis in T-ALL cells. As a proof of concept, immature and KMT2A-R T-ALL cells are vulnerable to pharmacological targeting of the interaction of RUNX2 with its co-factor CBFβ. In conclusion, we identify RUNX2 a dependency factor in immature and KMT2A-R T-ALL that regulates cell metabolism and disease progression
 
Overall design Examination of transcriptional changes upon in KARPAS-45 upon 24 hours treatment with 20 µM of the pan-RUNX inhibitor AI-10-104.
 
Contributor(s) Matthijssens F, Van Vlierberghe P
Citation(s) 33555272
Submission date Jun 04, 2020
Last update date Feb 10, 2021
Contact name Filip Matthijssens
E-mail(s) Filip.Matthijssens@UGent.be
Phone 093325268
Organization name Ghent University
Department Biomolecular Medicine
Lab Lab of normal and malignant hematopoesis
Street address Corneel Heymanslaan 10
City Ghent
State/province België
ZIP/Postal code 9000
Country Belgium
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (8)
GSM4591460 KPS_ctrl_rep1
GSM4591461 KPS_AI-10-104_rep1
GSM4591462 KPS_ctrl_rep2
This SubSeries is part of SuperSeries:
GSE151823 RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia
Relations
BioProject PRJNA637336
SRA SRP265979

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
GSE151821_rawCountMatrix_Runx2_inh.txt.gz 475.0 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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