GEO series

Highly specific immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in MLL-AF4-driven acute lymphoblastic leukemia.

GSE282470 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/04/10 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
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)

Proteasome inhibitors (PIs) Bortezomib, Carfilzomib and Ixazomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have clinical activity in acute lymphoblastic leukemia (ALL). The predominant form of proteasome in these hematologic malignancies is the lymphoid tissue specific immunoproteasome. FDA-approved PIs inhibit immunoproteasomes and ubiquitously expressed constitutive proteasomes causing on-target toxicities in non-hematological tissues.

Read the full summary ↓

Replacing PIs with selective immunoproteasome inhibitors (IPIs) should reduce these toxicities. We have previously shown that IPI ONX-0914 causes apoptosis of ALL cells expressing the MLL-AF4 fusion protein but did not elucidate the mechanism. Here we show that a novel, highly specific IPI M3258 induces rapid apoptosis in ALL cells in vitro and is comparable to bortezomib in its ability to reduce tumor growth and enhance effect of chemotherapy in vivo. Treatment of ALL cells with M3258, ONX-0914 and bortezomib induced proteotoxic stress that was prevented by the protein synthesis inhibitor cycloheximide, which dramatically desensitized cells to PI-induced apoptosis. Thus, like MM, ALL cells are sensitive to PIs and IPIs because they are under proteotoxic stress caused by elevated rates of protein synthesis.

This dataset

Open GSE282470 in finder → Find more human RNA-seq datasets → Acute lymphoblastic 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 GSE282470_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1188838 and SRA study SRP546647. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

A cohort of 12 individual samples

The grouping that defines any comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Sample titles run AK1 … AK12 and carry no group information.

Samples in this study

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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.