GEO DataSets

(Submitter supplied) Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: BW

(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

Platform:

GPL18573

20 Samples

Download data: BW

(Submitter supplied) Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: BW

(Submitter supplied) Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

8 Samples

Download data: BW

(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) 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) 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) Activation of GFI1-super-enhancer (GFI1-SE) by a LSD1 inhibitor NCD38 was relevant to myeloid differentiation and antileukemia effect in human erythroleukemia cells (HEL cells). Thus, we investigated the role of GFI1-SE upon NCD38 treatment in HEL cells. We established three independent sublines with bi-allelic deletion of GFI1-SE (CCE2 #114, #141, and #216) using CRISPR-Cas9 genome editing system in HEL cells and a classical limiting dilution method. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

12 Samples

Download data: CEL, CHP

(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:

GPL11154 GPL9115

34 Samples

Download data: BED

(Submitter supplied) The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors . In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells through degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knock-out, but LSD1 inhibition sensitizes them to physiological doses of RA without altering the stability of PML-RAR, and extends survival of leukemic mice upon RA treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL9115 GPL11154

9 Samples

Download data: TXT