GEO series
A dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia [CUT&RUN]
GSE253137
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
12 samples
Submitted 2024/10/20
Platform GPL20795Platform GPL21273
Summary
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Although intensified therapeutic protocols have improved the outcome of T-ALL patients, they coincide with severe short- and long-term side effects. In addition, no salvage therapeutic strategies are available for primary therapy-resistant or relapsed T-ALL, resulting in a dismal outcome for these patients. It highlights the need to identify new targets in T-ALL biology that allow the development of less toxic targeted therapies. PSIP1, a histone mark reader, is a dependency factor in KMT2A-rearranged myeloid leukemia, but is dispensable for normal hematopoiesis, making it an attractive therapeutic target. Nonetheless, rare recurrent inactivating mutations and deletions of PSIP1, suggest that PSIP1 could act as a tumor suppressor in T-ALL. Here, we demonstrate that the loss of Psip1 accelerates T-ALL initiation in mice and we identified a correlation with reduced H3K27me3 binding. Contrastingly, loss of PSIP1 impaired cell proliferation in several human and murine T-ALL cell lines. In these cell lines, PSIP1 loss leads to a significant downregulation of COX20, an assembly factor of the cytochrome c oxidase in the mitochondria, and is associated with a reduction in mitochondrial respiration. Similarly to what was observed for PSIP1, loss of COX20 expression also leads to an impairment of proliferation in these T-ALL cell lines. These data corroborate that PSIP1 can exert a dual role in the context of T-ALL, either as a tumor suppressor gene during tumor initiation or as a dependency factor in tumor maintenance.
Published in
Demoen L, Matthijssens F, Reunes L et al.
· Science advances 2024
· PMID 39485844
· doi:10.1126/sciadv.ado6765
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE253137_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1064101 and SRA study SRP483396. Searching any of these in the dataset finder brings you back here.
Study design
2 × CD2-iCre PSIP1 WT, H3K27me3, CUT&RUN, WT vs 2 × CD2-iCre PSIP1 WT, IgG, CUT&RUN, WT vs 2 × CD2-iCre PSIP1 KO, H3K27me3, CUT&RUN, KO vs 2 × CD2-iCre PSIP1 KO, IgG, CUT&RUN, KO
Supports a between-group comparison across 8 samples.
4 replicated groups read from 12 sample titles; they account for 8 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8014781 CD2-iCre PSIP1 WT, H3K27me3, CUT&RUN, WT1
- GSM8014782 CD2-iCre PSIP1 WT, IgG, CUT&RUN, WT1
- GSM8014783 CD2-iCre PSIP1 WT, H3K27me3, CUT&RUN, WT2
- GSM8014784 CD2-iCre PSIP1 WT, IgG, CUT&RUN, WT2
- GSM8014785 CD2-iCre PSIP1 KO, H3K27me3, CUT&RUN, KO1
- GSM8014786 CD2-iCre PSIP1 KO, IgG, CUT&RUN, KO1
- GSM8014787 CD2-iCre PSIP1 KO, H3K27me3, CUT&RUN, KO2
- GSM8014788 CD2-iCre PSIP1 KO, IgG, CUT&RUN, KO2
- GSM8014789 Jurkat, PSIP1, CUT&RUN
- GSM8014790 Jurkat, IgG (PSIP1-matched control), CUT&RUN
- GSM8014791 Jurkat, H3K36me3, CUT&RUN
- GSM8014792 Jurkat, IgG (H3K36me3-matched control), CUT&RUN
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