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Targeting LMO2-induced autocrine FLT3 signalling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia [ChIP-seq]

GSE264576 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2026/04/30 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 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 lymphoblastic leukemiaThis series is part of our curated briefing on it.
Samples
12 samples
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)
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) characterised by aberrant expression of the LMO2-LYL1 stem cell transcription factor complex, activating mutations of cytokine receptor signalling and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence.
Read the full summary ↓
Here, analyses of Lmo2 transgenic mice, patient-derived xenografts and single cell RNA-seq data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells co-expressing the cytokine receptors c-KIT and FLT3 (KF cells). Despite a highly proliferative state, these KF cells had long-term self-renewal capacity and almost complete resistance to chemotherapy. Chromatin immunoprecipitation and assay for transposase-accessible chromatin sequencing demonstrated FLT3 and its ligand may be direct targets of the LMO2 stem-cell complex. Media conditioned by Lmo2 transgenic thymocytes revealed an autocrine FLT3-dependent signalling loop that could be targeted by the FLT3 inhibitor Gilteritinib. Consequently, Gilteritinib impaired in vivo growth of ETP-ALL and improved the response to chemotherapy. Furthermore, Gilteritinib synergized with the BCL2 inhibitor Venetoclax, which may enable ‘chemo-free’ treatment of ETP-ALL. Together, these data provide a cellular and molecular explanation for enhanced cytokine signalling in LMO2-driven T-ALL beyond activating mutations and a rationale for clinical trials of FLT3 inhibitors in ETP-ALL.
This dataset
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.

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 GSE264576_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1103177 and SRA study SRP503375. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

More Acute lymphoblastic leukemia datasets

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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.