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Series GSE151819 Query DataSets for GSE151819
Status Public on Jun 05, 2020
Title RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [RUNX2 ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy 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 RUNX2 genomewide binding and H3K27acetylation in two T-ALL cell lines
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
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 (7)
GSM4591423 KPS_input
GSM4591424 KPS_RUNX2_ChipSeq
GSM4591425 KPS_H3K27ac
This SubSeries is part of SuperSeries:
GSE151823 RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia
BioProject PRJNA637334
SRA SRP265977

Download family Format
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Supplementary file Size Download File type/resource
GSE151819_RAW.tar 4.5 Mb (http)(custom) TAR (of BED, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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