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BPDCN MYB Fusions Regulate Cell Cycle Genes, Impair Differentiation and Induce Myeloid-Dendritic Cell Leukemia [HoxCutRun]

GSE261666 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 27 samples Submitted 2024/11/15 Platform GPL19057
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 27 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
Mus musculus (mouse)
Samples
27 samples: 21 distinct titles, 6 of them repeatedGroups 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.
Paper
BPDCN MYB fusions regulate cell cycle genes, impair differentiation, and induce myeloid-dendritic cell leukemiaJCI insight · 2024
Summary (written by the submitters)
MYB fusions are recurrently found in select cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), an acute leukemia with poor prognosis. They are markedly enriched in BPDCN compared to other blood cancers, and in some patients are the only obvious somatic mutation detected. This suggests they may alone be sufficient to drive dendritic cell transformation.
Read the full summary ↓
MYB fusions are hypothesized to alter the normal transcription factor activity of MYB, but mechanistically how they promote leukemogenesis is poorly understood. Using CUT&RUN chromatin profiling, we found that in BPDCN leukemogenesis, MYB switches from being a regulator of dendritic cell lineage genes to aberrantly regulating G2/M cell cycle control genes. MYB fusions found in BPDCN patients increased the magnitude of DNA binding at these locations, and this was linked to BPDCN-associated gene expression changes. Furthermore, expression of MYB fusions in vivo impaired dendritic cell differentiation and induced transformation to generate a mouse model of myeloid-dendritic acute leukemia. Therapeutically, we present evidence that all-trans retinoic acid (ATRA) may cause loss of MYB protein and cell death in BPDCN.
Published in
BPDCN MYB fusions regulate cell cycle genes, impair differentiation, and induce myeloid-dendritic cell leukemia
Booth CAG, Bouyssou JM, Togami K et al. · JCI insight 2024 · PMID 39499902 · doi:10.1172/jci.insight.183889
This dataset
Open GSE261666 in finder → Find more mouse ChIP / ATAC / CUT&Tag datasets →
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 GSE261666_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 PRJNA1088234 and SRA study SRP495354. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39499902) ↗
Study design
21 distinct titles, 6 of them repeated
Hoxb8 MS5, Cdkn2a-KO MYB-PLEKHO1, V5 ×2 Hoxb8 MS5, Cdkn2a-KO MYB-TR, V5 ×2 Hoxb8 MS5, Cdkn2a-KO MYB-WT, V5 ×2 Hoxb8 MS5, Cdkn2a-WT MYB-PLEKHO1, V5 ×2 Hoxb8 MS5, Cdkn2a-WT MYB-TR, V5 ×2 Hoxb8 MS5, Cdkn2a-WT MYB-WT, V5 ×2

How we read this: Read from 27 sample titles: 21 distinct titles with little repetition. 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
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