GEO DataSets

(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

(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) Preclinical studies have shown that combining the LSD1 inhibitor tranylcypromine (TCP) with all-trans retinoic acid (ATRA) induces differentiation and impairs survival in non-APL acute myeloid leukemia (AML). We conducted a Phase 1 clinical trial (NCT02273102) to evaluate the safety and preliminary activity of ATRA in combination with TCP in patients with relapsed/refractory AML and myelodysplasia (MDS). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

30 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

Platform:

GPL16791

36 Samples

Download data: BIGWIG

(Submitter supplied) We investigate the effects of GCN5 and LSD1 inhibition in acute myeloid leukemia. Therefore, we characterized gene expression changes by RNA-seq in AML cells (AML M2 cell line HL-60) following treatment with ATRA, MB3, GSK-LSD1 and their combinations.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

21 Samples

Download data: XLS

(Submitter supplied) We investigate the effects of GCN5 and LSD1 inhibition in acute myeloid leukemia. Therefore, we characterized acetylation and di-methylation changes by ChIP-seq in AML cells (AML M2 cell line HL-60) following treatment with ATRA, MB3, GSK-LSD1 and their combinations.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

15 Samples

Download data: BIGWIG

(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

(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:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL9115

25 Samples

Download data: BED

(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:

GPL18573 GPL16791 GPL19604

28 Samples

Download data: CSV, TXT

(Submitter supplied) Combined treatment with all-trans retinoic acid and GSK2879552 results in synergistic effects on gene expression, cell proliferation, markers of differentiation, and, most importantly, cytotoxicity.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

96 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) The canonical function of EZH2 is methylation of H3K27, although important non-canonical roles have recently been described. EZH2 mutation or deregulated expression has been conclusively demonstrated in the pathogenesis and response to treatment of acute myeloid leukemia (AML), thus making it an attractive therapeutic target. In this study, we therefore investigated whether inhibition of EZH2 might also improve the response of non-APL AML cells to ATRA-based therapy. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

42 Samples

Download data: CEL, CHP

(Submitter supplied) The lysine-specific demethylase LSD1/KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). Inhibition of its expression or catalytic activity overcomes the differentiation block and reduces colony formation potential. We have developed ORY-1001 as highly potent and selective inhibitor of KDM1A. Treatment of AML cell lines with ORY-1001 induces accumulation of H3K4me2 marks at KDM1A target genes, compromises leukemic stem cell capacity, and provokes blast differentiation. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL23032

54 Samples

Download data: TXT

(Submitter supplied) We report the use of RNAseq to determine genomewide transcriptional changes induced by all-trans retinoic acid differentiation of NB4 acute promyelocytic leukemia (APL) cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL15433

4 Samples

Download data: TXT

(Submitter supplied) We report the use of RNAseq to determine the role of the TFEB transcription factor in all-trans retinoic acid induced differentiation of NB4 acute promyelocytic leukemia (APL) cells. We used lentiviral mediated shRNA approaches to functionally deplete TFEB in NB4 cells and compared the transcriptomes of wild type, scramble control shRNA and shTFEB knockdown cells treated with ethanol (control) versus all-trans retinoic acid for 72 hours.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL15433

8 Samples

Download data: TXT

(Submitter supplied) Acute myeloid leukemia (AML) is characterized by an accumulation of aberrant myeloid cells arrested at different stages of differentiation. Therapeutic approaches that prompt AML blasts to differentiate represent an attractive opportunity in the landscape of AML therapies, as they aim to induce terminal maturation and leukemia debulking without intensive cytotoxic treatments. In the present study, we investigate the involvement of HIF1a and HIF2a transcription factors in AML pathogenesis, and position HIF2a as a novel regulator of the AML differentiation block. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

8 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:

GPL24676

32 Samples

Download data: BW

(Submitter supplied) Acute myeloid leukemia (AML) is characterized by an accumulation of aberrant myeloid cells arrested at different stages of differentiation. Therapeutic approaches that prompt AML blasts to differentiate represent an attractive opportunity in the landscape of AML therapies, as they aim to induce terminal maturation and leukemia debulking without intensive cytotoxic treatments. In the present study, we investigate the involvement of HIF1 and HIF2 transcription factors in AML pathogenesis, and position HIF2 as a novel regulator of the AML differentiation block. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

6 Samples

Download data: BW