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Effect of 48h treatment with 100nM GSK2879552 on T-ALL cell lines LOUCY and PEER

ABSTRACT: RNA sequencing was performed on biological triplicates of LOUCY and PEER cells treated with 100nM GSK2879552 for 48h versus their corresponding DMSO treatment controls. GSK2879552 is a potent, selective and orally bioavailable inhibitor of the lysine-specific histone demethylase 1 (LSD1). Gene expression was severely affected by LSD1 inhibition. Pathway analysis performed on the differentially expressed genes following 48hrs of LSD1i treatment clearly showed an increased apoptotic gene signature (CASP3, CASP8) and enhanced expression of genes associated with TRAIL signaling. Furthermore, pre-ranked Gene Set Enrichment Analysis (GSEA) revealed that genes upregulated after LSD1 inhibition in LOUCY showed significant enrichment for transcripts that are down in hematopoietic stem cells and early T lymphocytes. In contrast, important components of the Notch, WNT and SMAD signalling complex were significantly down regulated upon short-term LSD1i treatment in LOUCY cells. In line with this notion, pre-ranked GSEA also revealed that LSD1i resulted in decreased expression of genes that significantly overlap with an oncogenic MYC signature.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83126 | GEO | 2017/02/03

SECONDARY ACCESSION(S): PRJNA324827

REPOSITORIES: GEO

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Effect of 48h treatment with 100nM GSK2879552 on T-ALL cell lines HSB2 and RPMI8402

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

Project description: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.

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Gene expression signature of the T-ALL cell line LOUCY treated with 250nM (+)-JQ1 for 4h

Project description:We analyzed the transcriptional consequences of the BET bromodomain inhibitor JQ1 in the T-ALL cell line LOUCY by microarray analysis. Short-term exposure to a low dose of JQ1 (4h, 250nM) provided insights in the genes whose expression was immediately affected by BET bromodomain inhibition. Significantly downregulated genes upon short-term drug treatment included stem-cell associated genes and putative oncogenes such as BAALC, WT1, MN1, MEF2C, LMO1 and LMO2. Genes associated with the 500 highest ranked enhancer regions in LOUCY, were significantly enriched in genes downregulated after JQ1 treatment.

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Homo sapiens

Project description:Effect of 48h treatment with 100nM GSK2879552 on T-ALL cell lines LOUCY and PEER

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H3K27ac ChIP-Seq in LOUCY

Project description:H3K27ac ChIP-Seq data of the T-ALL cell line LOUCY was obtained to find active regions in the genome and to correlate that with expression profiling of lncRNAs in the LOUCY cell line. ChIP-sequencing data was generated for H3K27ac in the T-ALL cell line LOUCY.

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H3K27ac ChIP-Seq in LOUCY

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Gene Expression Analyisis of T-ALL LOUCY cell lines treated with ETV6 siRNA vs. scramble control siRNA

Project description:Transcriptional effects of ETV6 inactivation in immature T-ALL were investigated by gene expression analysis upon siRNA-mediated knockdown of ETV6 in LOUCY cells, a T-ALL cell line with a transcriptional program highly related to that of immature T-ALLs. Gene Set Enrichment Analysis (GSEA) of the ETV6 knockdown signature showed a significant enrichment in genes characteristically upregulated in ETV6 mutant immature T-ALLs including HOXA13, PRDM16, PTEN and CD33. 4 samples were analyzed: two biological replicates for each experimental group.

2011-11-24 | E-GEOD-33820 | biostudies-arrayexpress

A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC (microarray)

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2015-07-14 | E-GEOD-66294 | biostudies-arrayexpress

Gene Expression Analyisis of T-ALL LOUCY cell lines treated with ETV6 siRNA vs. scramble control siRNA

2011-11-24 | GSE33820 | GEO

A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC (ChIP-Seq)

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2015-07-14 | E-GEOD-66297 | biostudies-arrayexpress

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