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Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [RNA-seq]

ABSTRACT: Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [RNA-seq]

PROVIDER: PRJNA844549 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19520258_1.fastq.gz	Fastqsanger.gz
	SRR19520258_2.fastq.gz	Fastqsanger.gz
	SRR19520259_1.fastq.gz	Fastqsanger.gz
	SRR19520259_2.fastq.gz	Fastqsanger.gz
	SRR19520260_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation

Project description:Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation

| PRJNA844546 | ENA

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [ChIP-seq]

Project description:Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [ChIP-seq]

| PRJNA844550 | ENA

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [RNA-seq]

Project description:The epigenomic effects of maltonis, a novel maltol-derived molecule with promising antiproliferative activity against leukemic cells, have been characterized in the APL NB4 cell line. We demonstrate that maltonis treatments induce a profound remodulation of the histone code, reducing global H3K9me3 signal and modulating other histone post-translational modifications (HPTMs). Transcriptomic and epigenomic analyses revealed that maltonis exposure of NB4 cells induces changes in the expression of hundreds of genes (551 upregulated and 288 downregulated) in association with the modulation of the permissive HPTMs histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac) at their gene promoters. The upregulation of interferon alpha and gamma and the downregulation of c-MYC target genes have been identified as most significant pathways modulated by maltonis. Most importantly, c-MYC is strongly downregulated by maltonis and represents the common denominator of the downregulated gene sets, suggesting a central role of this gene in the biological response of NB4 cells to maltonis.

2022-12-15 | GSE205345 | GEO

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [ChIP-seq]

2022-12-15 | GSE205344 | GEO

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation.

Project description:Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML) in which the PML/RARα fusion protein exerts oncogenic activities by recruiting repressive complexes to the promoter of specific target genes. Other epigenetic perturbations, as alterations of histone H3 lysine 9 trimethylation (H3K9me3), have been frequently found in AMLs and are associated with leukemogenesis and leukemia progression. Here, we characterized the epigenomic effects of maltonis, a novel maltol-derived molecule, in APL cells. We demonstrate that maltonis treatments induce a profound remodulation of the histone code, reducing global H3K9me3 signal and modulating other histone post-translational modifications. Transcriptomic and epigenomic analyses revealed that maltonis exposure induces changes of genes expression associated with a genomic redistribution of histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 acetylation (H3K27ac). Upregulation of interferon alpha and gamma response and downregulation of c-MYC target genes, in function of c-MYC reduced expression (monitored in all the hematopoietic neoplasms tested), represent the most significant modulated pathways. These data demonstrate the ability of maltonis to epigenetically reprogram the gene expression profile of APL cells, inducing an intriguing antiviral-like response, concomitantly with the downregulation of c-MYC-related pathways, thus making it an attractive candidate for antileukemic therapy.

| S-EPMC10191840 | biostudies-literature

Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-15 | GSE205346 | GEO

Transcriptome array of Pml+/+ and Pml-/- mice APL cells treated with ATRA+ATO against untreated controls

Project description:This experiment aims at understanding the main transcriptomic basals differences between Pml+/+ and Pml-/- APL blasts and during ATRA+ATO treatment. Mice were transplanted were Pml+/+ or Pml-/- blasts. Once sick, mice were treated with 12 hours of ATRA+ATO therapy (ATRA: subcutaneous diffusion, ATO: intraperitoneal injection). After treatment, bone marrow cells were harvested and blasts were sorted (GFP blasts used). After sorting, cells were frozen at -80°C (in RNA lysis buffer). Then, RNA was extracted with the Qiagen RNeasy Minikit. Samples were then hybridized on MTA 1.0 chips.

2025-01-01 | E-MTAB-13392 | biostudies-arrayexpress

Gene Expression-Based High Throughput Screening: APL Treatment with Candidate Compounds

Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes. Keywords = Leukemia Keywords = APL Keywords = AML Keywords = chemical genomics Keywords: repeat sample

2004-01-30 | GSE976 | GEO

Transcription profiling of blasts from three APL patients expressing PML/RAR before and after treatment with 1 uM retinoic acid (RA) in vitro for four hours

Project description:Gene expression profiles in blasts from three APL patients expressing PML/RAR were assessed before and after treatment with 1 uM retinoic acid (RA) in vitro for four hours. We then studied a U937 clone conditionally expressing PML/RAR (U937-PR), (Grignani et al. 1993) (Alcalay et al. 2003), and compared the gene expression profile prior to and after 4 hours of treatment with 1 uM RA, to that obtained from a cell line bearing an empty vector (U937-MT). For each sample, biotinylated cRNA targets were synthesized starting from 5ug of total RNA, and hybridized to the complete set of HG-U133 Affymetrix oligonucleotide chips, which explores the expression of approximately 45,000 human transcripts. Results were analyzed using MASv5 and further elaborated with the GenePicker software. GeneChip probe sets regulated by RA in each sample were clustered into non-redundant regulated genes according to UniGene release Hs.166.

2004-12-31 | E-MEXP-149 | biostudies-arrayexpress

Targets of ALTERED PHLOEM DEVELOPMENT (APL)

Project description:We profiled transcripts from sorted phloem cells of wild-type and apl mutants to identify the genes regulated by APL in phloem. We profiled transcripts from sorted phloem cells of wild-type and apl mutants to identify the genes regulated by APL in phloem.

2014-08-25 | GSE55222 | GEO

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