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Integrated Multi-Omics and Interactome Analysis of CDK8 Inhibition Reveals Erythroid Differentiation Programs and BET Synergy in AML Stem-like Cells

GSE319092 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 135 samples Submitted 2026/05/31 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 135 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Topic
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
135 samples: 40 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Acute myeloid leukemia (AML) with leukemic stem cell (LSC) characteristics represents a therapeutic challenge due to inherent resistance to differentiation. CDK8, a kinase component of the Mediator complex, has emerged as a regulator of oncogenic transcription, yet its role in LSC maintenance and potential as a combination therapy target remains incompletely defined.
Read the full summary ↓
RVU120 (Romaciclib) and CCT251921 are selective, orally bioavailable small-molecule inhibitors of CDK8. Of them, RVU120 is currently tested as monotherapy in stage II clinical trials for Myelodysplastic Syndrome. Here, we demonstrate that pharmacologic CDK8 inhibition rapidly suppresses STAT5 Ser726 phosphorylation in LSC-like TEX cells, reduces CD34+ populations, and drives erythroid/megakaryocytic differentiation. Integrated time-resolved transcriptomic, proteomic, and phosphoproteomic analyses of TEX cells, revealed highly concordant responses to both inhibitors, with progressive activation of cholesterol biosynthesis, inflammatory signaling, and erythroid-like differentiation. Phosphoproteomic profiling identified a restricted set of altered phosphosites enriched in nucleic acid-binding proteins. Co-immunoprecipitation mass spectrometry mapping of the CDK8 interactome in TEX and AML models identified core proteins, including Mediator components, chromatin remodelers (INO80), and BRD3, a BET family bromodomain protein. CUT&Tag genomic profiling demonstrated that CDK8 inhibition triggers widespread enhancer activation (H3K27ac, H3K4me1) with coordinated redistribution of Polymerase II RNA, BRD3, and MLL4, while uncoupling proliferative from immune-regulatory chromatin programs. Functional screening revealed context-dependent synergy between CDK8 and BET inhibition in AML cell lines and patient-derived xenograft models. These findings position CDK8 as a central node in LSC transcriptional control and establish a mechanistic rationale for combined CDK8-BET inhibition as a precision therapeutic strategy in molecularly defined AML subsets.
This dataset
Open GSE319092 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Acute myeloid leukemia landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE319092_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1422091 and SRA study SRP676238. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
40 conditions, mostly in triplicate
MLL4_DMSO_T0 ×4 BRD3_DMSO_T0 ×4 NFRKB_DMSO_T0 ×4 MLL4_RVU120_24h ×4 BRD3_RVU120_24h ×4 NFRKB_RVU120_24h ×4 MLL4_RVU120_72h ×4 BRD3_RVU120_72h ×4 +32 more

Supports a between-group comparison across 135 samples.

How we read this: 40 replicated groups read from 135 sample titles; they account for 135 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 95 more — browse all 135 samples with per-sample file links →

More Acute myeloid leukemia datasets

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.