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Series GSE101821 Query DataSets for GSE101821
Status Public on Mar 02, 2018
Title The novel BETi BI 894999 represses super-enhancer associated transcription and synergizes with CDK9 inhibition in AML by induction of apoptosis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Bromodomain and extra-terminal (BET) protein inhibitors have been reported as treatment options for acute myeloid leukemia (AML) in preclinical models and are currently being evaluated in clinical trials. This work presents a novel potent and selective BET inhibitor (BI 894999), which has recently entered clinical trials (NCT02516553). In preclinical studies, this compound is highly active in AML cell lines, primary patient samples, and xenografts. HEXIM1 is described as an excellent pharmacodynamic biomarker for target engagement in tumors as well as in blood. Mechanistic studies show that BI 894999 targets super-enhancer-regulated oncogenes and other lineage-specific factors, which are involved in the maintenance of the disease state. BI 894999 is active as monotherapy in AML xenografts, and in addition leads to strongly enhanced antitumor effects in combination with CDK9 inhibitors. This treatment combination results in a marked decrease of global p-Ser2 RNA polymerase II levels and leads to rapid induction of apoptosis in vitro and in vivo. Together, these data provide a strong rationale for the clinical evaluation of BI 894999 in AML.
 
Overall design We performed ChIP-seq experiments in 22 samples covering 4 different cell lines and 3 different antibodies (H3K27ac, BRD4, RNA Pol-II). Some experiments were performed using 2 biological replicates. Technical replicates (if available) were merge in the respective FASTQ files. All published ChIP-seq results were derived from merged biological replicates for the specific ChIP-seq experiment with respect to the cell line specific input. Unique numbers in the sample/result names assign the FASTQ files to their processed output files. We also performed Quant-seq in-vivo experiments in 27 cell-line derived xenografts (MV-4-11-B) using 3-4 replicates. Control samples are detonated as the Natrosol treated samples. Lastly, we performed RNA-seq experiments in 38 samples covering 6 different cell lines. These experiments were performed using 2 biological replicates. Note, the compound mentioned in the paper LDC000067 is identical to EX00101218 - these are two different identifiers for the same molecule.
 
Contributor(s) Gerlach D, Savarese F, Schweifer N, Kaya O, Beck J
Citation(s) 29491412
Submission date Jul 24, 2017
Last update date Nov 02, 2021
Contact name Daniel Gerlach
E-mail(s) daniel.gerlach@boehringer-ingelheim.com
Organization name Boehringer Ingelheim RCV GmbH & Co KG
Department Global Computational Biology and Digital Sciences
Street address Dr.-Boehringer-Gasse 5-11
City Vienna
ZIP/Postal code 1121
Country Austria
 
Platforms (2)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (101)
GSM2716691 ChIPseq_MOLM-13_H3K27ac_NA_NA_NA_NA_NA_NA_rep1_J4760
GSM2716692 ChIPseq_MOLM-13_INPUT_NA_NA_NA_NA_NA_NA_rep1_J4762
GSM2716693 ChIPseq_MV-4-11-B_BRD4_BI00894999_1000nM_4h_NA_NA_NA_rep1_J3756
Relations
BioProject PRJNA395584
SRA SRP113492

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE101821_ChIPseq_MOLM-13_H3K27ac_NA_NA_NA_NA_NA_NA_NA_J4760-J4762_peaks.tsv.gz 124.3 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_BRD4_BI00894999_1000nM_4h_NA_NA_NA_NA_J3756-J2596-J2605_peaks.tsv.gz 161 b (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_BRD4_BI00894999_100nM_4h_NA_NA_NA_NA_J3758-J2596-J2605_peaks.tsv.gz 128.9 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_BRD4_BI00894999_1nM_4h_NA_NA_NA_NA_J2600-J2609-J3762-J2596-J2605-J3766_peaks.tsv.gz 181.7 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_BRD4_BI00894999_35nM_4h_NA_NA_NA_NA_J2601-J2610-J3760-J2596-J2605-J3766_peaks.tsv.gz 130.2 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_BRD4_DMSO_NA_NA_NA_NA_NA_NA_J2608-J2778-J3764-J2596-J2605-J3766_peaks.tsv.gz 166.0 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_H3K27ac_NA_NA_NA_NA_NA_NA_NA_J3765-J2596-J2605_peaks.tsv.gz 217.6 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_POLII_BI00894999_35nM_4h_EX00101218_5uM_4h_NA_J5933-J2596-J2605-J3766_peaks.tsv.gz 120.9 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_POLII_BI00894999_35nM_4h_NA_NA_NA_NA_J5929-J2596-J2605-J3766_peaks.tsv.gz 126.2 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_POLII_DMSO_NA_NA_NA_NA_NA_NA_J5927-J2596-J2605-J3766_peaks.tsv.gz 57.3 Kb (ftp)(http) TSV
GSE101821_ChIPseq_MV-4-11-B_POLII_EX00101218_5uM_4h_NA_NA_NA_NA_J5931-J2596-J2605-J3766_peaks.tsv.gz 121.4 Kb (ftp)(http) TSV
GSE101821_ChIPseq_NCI-H2171_BRD4_NA_NA_NA_NA_NA_NA_NA_J2386-J2374_peaks.tsv.gz 32.7 Kb (ftp)(http) TSV
GSE101821_ChIPseq_NCI-H2171_H3K27ac_NA_NA_NA_NA_NA_NA_NA_J2377-J2388-J2374-J2385_peaks.tsv.gz 273.0 Kb (ftp)(http) TSV
GSE101821_ChIPseq_OCI-AML3_H3K27ac_NA_NA_NA_NA_NA_NA_NA_J4772-J4774_peaks.tsv.gz 244.2 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_BI00894999_1mgkg_2h_Flavopiridol_2.5mgkg_2h_NA_J5698-J5757-J5811-J5865-J5714-J5746-J5800_dge.tsv.gz 958.6 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_BI00894999_1mgkg_2h_NA_NA_NA_NA_J5694-J5753-J5807-J5861-J5714-J5746-J5800_dge.tsv.gz 936.6 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_BI00894999_1mgkg_6h_Flavopiridol_2.5mgkg_6h_NA_J5703-J5762-J5816-J5870-J5714-J5746-J5800_dge.tsv.gz 981.1 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_BI00894999_1mgkg_6h_NA_NA_NA_NA_J5699-J5758-J5812-J5866-J5714-J5746-J5800_dge.tsv.gz 925.1 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_Flavopiridol_2.5mgkg_2h_NA_NA_NA_NA_J5696-J5755-J5809-J5863-J5714-J5746-J5800_dge.tsv.gz 939.7 Kb (ftp)(http) TSV
GSE101821_QUANTseq_MV-4-11-B_NA_Flavopiridol_2.5mgkg_6h_NA_NA_NA_NA_J5701-J5760-J5814-J5868_dge.tsv.gz 942.6 Kb (ftp)(http) TSV
GSE101821_Quantseq_MV-4-11-B_NA_BI00894999_100nM_4h_NA_NA_NA_NA_J11985-J11986-J11987-J11974-J11975_dge.tsv.gz 901.0 Kb (ftp)(http) TSV
GSE101821_Quantseq_MV-4-11-B_NA_BI00894999_10nM_4h_NA_NA_NA_NA_J11982-J11983-J11984-J11974-J11975_dge.tsv.gz 890.5 Kb (ftp)(http) TSV
GSE101821_Quantseq_MV-4-11-B_NA_JQ1_2000nM_4h_NA_NA_NA_NA_J11979-J11980-J11981-J11974-J11975_dge.tsv.gz 890.3 Kb (ftp)(http) TSV
GSE101821_Quantseq_MV-4-11-B_NA_JQ1_200nM_4h_NA_NA_NA_NA_J11976-J11977-J11978-J11974-J11975_dge.tsv.gz 888.4 Kb (ftp)(http) TSV
GSE101821_RNAseq_HL-60_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J4251-J4255-J4250-J4254_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_KASUMI-1_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J4227-J4231-J4226-J4230_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MOLM-13_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J4242-J4246-J4249-J4245_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_1000nM_4h_NA_NA_NA_NA_J3914-J3919-J3910-J3915_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_100nM_4h_NA_NA_NA_NA_J3913-J3918-J3910-J3915_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_1nM_4h_NA_NA_NA_NA_J3911-J3916-J3910-J3915_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_35nM_4h_EX00101218_5uM_4h_NA_J4197-J4205-J4194-J4202_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J3912-J3917-J3910-J3915_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J4195-J4203-J4194-J4202_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_MV-4-11-B_NA_EX00101218_5uM_4h_NA_NA_NA_NA_J4196-J4204-J4194-J4202_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
GSE101821_RNAseq_NCI-H2171_NA_BI00894999_100nM_4h_NA_NA_NA_NA_J4146-J4154-J4147-J4155_dge.tsv.gz 2.9 Mb (ftp)(http) TSV
GSE101821_RNAseq_OCI-AML3_NA_BI00894999_35nM_4h_NA_NA_NA_NA_J4235-J4239-J4234-J4238_dge.tsv.gz 2.8 Mb (ftp)(http) TSV
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