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Effect of 24h treatment with 100nM GSK2879552 on the murine T-ALL cell with and without Zeb2 overexpression

ABSTRACT: RNA sequencing was performed on biological triplicates of p53 null T-ALL cells with ZEB2 overexpression (P53/R26-Zeb2tg/tg) versus p53 null T-ALL cells without Zeb2 overexpression (P53/R26+/+) treated with 100nM GSK2879552 for 24h versus their corresponding DMSO treatment controls. P53/R26+/+ and P53/R26-Zeb2tg/tg tumor lines displayed a very distinct gene expression signature under baseline (DMSO) conditions in line with our previous observations that Zeb2 driven thymomas reflect a more immature T-ALL subtype. GSK2879552 is a potent, selective and orally bioavailable inhibitor of the lysine-specific histone demethylase 1 (LSD1). LSD1i treatment in control P53/R26+/+ cell lines only caused limited effects on overall transcription. In contrast, gene transcription was more severely affected by LSD1 perturbations in the P53/R26-Zeb2tg/tg lines with significant changes in the expression transcripts enriched for signalling pathways essential for embryonic development (like TGFbeta and Wnt signalling), genes involved in transcriptional repression/regulation, apoptosis and DNA replication/repair. All together, these results demonstrate that Zeb2 overexpression modulates murine T-ALL responsiveness to LSD1 inhibitors.

ORGANISM(S): Mus musculus

PROVIDER: GSE83127 | GEO | 2017/02/03

SECONDARY ACCESSION(S): PRJNA324826

REPOSITORIES: GEO

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