GEO DataSets

(Submitter supplied) Lsd1KO and ATRA treatment in Hoxa9/Meis1- and MN1-transformed myeloid progenitor cells LSD1 has emerged as a promising epigenetic target in the treatment of acute myeloid leukemia (AML). Inhibition of LSD1 has been shown to induce differentiation and facilitate the responsiveness of AML cells to all-trans retinoic acid. We used two murine AML models based on retroviral overexpression of Hoxa9/Meis1 (H9M) or MN1 to study the effect of Lsd1 knockout in AML. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL17021

26 Samples

Download data: BED, TXT, XLSX

(Submitter supplied) To determine whether changes in histone modifications directly correlate with changes in transcription, THP1 AML cells were treated with a potent and selective LSD1 inhibitor (OG86, 250nM) and then subjected to concomitant RNA sequencing (RNAseq) and ChIP sequencing (ChIPseq) for histone acetylation modifications, RCOR1, SPI1 and MLL4.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

10 Samples

Download data: BW

(Submitter supplied) To identify regions of genome accessibility influenced by LSD1 inhibition, THP1 AML cells were subjected to ATAC sequencing.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

2 Samples

Download data: TXT

(Submitter supplied) To identify genomic binding regions, THP1 AML cells were subjected to ChIP sequencing (ChIPseq) using anti-LSD1, MYB or GFI1 antibodies.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16558 GPL18573 GPL16791

28 Samples

Download data: BW, TXT

(Submitter supplied) To determine whether changes in histone modifications directly correlate with changes in transcription, THP1 AML cells were treated with a potent and selective LSD1 inhibitor (OG86) and then subjected to concomitant RNA sequencing (RNAseq) and ChIP sequencing (ChIPseq) for monomethyl-, dimethyl- and trimethyl histone H3 modifications.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: TXT

(Submitter supplied) To determine whether changes in histone modifications directly correlate with changes in transcription, THP1 AML cells were treated with a potent and selective LSD1 inhibitor (OG86) and then subjected to concomitant RNA sequencing (RNAseq) and ChIP sequencing (ChIPseq) for monomethyl-, dimethyl- and trimethyl histone H3 modifications.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16558

4 Samples

Download data: TXT

(Submitter supplied) Lysine Specific Demethylase 1 (LSD1 or KDM1A) is one of a number of epigenetic regulators which have recently emerged as candidate therapeutic targets in acute myeloid leukaemia (AML). Pharmacological inhibitors of LSD1 such as the tranylcypromine derivatives have already commenced evaluation in early phase clinical trials; however like all acute leukaemia therapies, it is unlikely that these inhibitors are effective as single agents. more...

Organism:

synthetic construct; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL16791 GPL18573 GPL19604

28 Samples

Download data: CSV, TXT

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We evaluated a pre-treatment bone marrow sample of a patient who showed a clinical response to INCB059872 + azacitidine treatment. Single-cell RNA-sequencing (scRNA-seq) showed that INCB059872 caused a shift in gene expression that was associated with GFI1/GFI1B regulation.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

8 Samples

Download data: MTX, TSV

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. Mice treated with INCB059872 had reduced platelet counts within 4 days of treatment. Here, we used single-cell RNA-seq to study the effects of INCB059872 on hematopoietic progenitor populations within wild-type murine bone marrow. Our results showed that INCB059872 triggered accumulation of megakaryocyte early progenitor cells with gene expression hallmarks of stem cells, which may begin to explain the thrombocytopenia observed in patients treated with LSD1 inhibitors.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

9 Samples

Download data: TAR

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We identified a population of cells within murine lineage-negative bone marrow that is expanded after treatment with INCB059872. Here we sorted cells from this population (Lin- Cd41+ Cd200r3-) and performed RNA-seq to measure gene expression changes caused by INCB059872. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: DIFF

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We performed ChIP-seq for histone modifications to define the earliest regulatory events associated with INCB059872 treatment. Changes in acetylation were more dramatic than changes in methylation, and these changes could be traced back to a loss of CoREST activity at GFI1-regulated targets.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24676 GPL18573

20 Samples

Download data: BEDGRAPH

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. LSD1 inhibition can induce differentiation of acute myeloid leukemia (AML), and here we have used RNA-seq to measure the transcriptional changes caused by INCB059872 in two AML cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

14 Samples

Download data: DIFF

(Submitter supplied) INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We used precision nuclear run-on sequencing (PRO-seq) to define early transcriptional changes associated with INCB059872 treatment. Changes in nascent transcription could be traced back to a loss of CoREST activity resulting in activation of GFI1-regulated targets.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL18573

8 Samples

Download data: BEDGRAPH

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus; Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

20 Samples

Download data: BW

(Submitter supplied) Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: BED, BW

(Submitter supplied) Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML. more...

Organism:

Mus musculus; Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

14 Samples

Download data: BED, BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL10558 GPL10999

40 Samples

Download data: BED

(Submitter supplied) All-trans-retinoic acid (ATRA) has been successfully used in therapy of acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML) but the response of non-APL AML cases to ATRA-based treatment has been poor. Here we show that, via epigenetic reprogramming, inhibitors of LSD1/KDM1 demethylase including tranylcypromine (TCP) unlocked the ATRA-driven therapeutic response in non-APL AML. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL10999

10 Samples

Download data: BED

(Submitter supplied) All-trans-retinoic acid (ATRA) has been successfully used in therapy of acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML) but the response of non-APL AML cases to ATRA-based treatment has been poor. Here we show that, via epigenetic reprogramming, inhibitors of LSD1/KDM1 demethylase including tranylcypromine (TCP) unlocked the ATRA-driven therapeutic response in non-APL AML. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

30 Samples

Download data: TXT