GEO series

ASS1 deficiency defines a therapeutic vulnerability in Philadelphia chromosome-positive acute lymphoblastic leukaemia

GSE330924 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/05/25 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: 3 × TOM-1, Control, vs 3 × TOM-1, ADI-PEG20, vs 3 × RS4;11, Control, vs 3 × RS4;11, ADI-PEG20,Groups 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)

Amino acid deprivation with L-asparaginase is a cornerstone of treatment in acute lymphoblastic leukaemia (ALL), but clinical challenges limit its use in adults. Deficiency in the enzyme argininosuccinate synthase (ASS1-low) confers arginine auxotrophy, defining a dependence on extracellular arginine, and represents an analogue metabolic vulnerability that is targetable through arginine deprivation.

Read the full summary ↓

We analysed transcriptomic data across >550 adult B-ALL cases to establish clinico-biologic characteristics of low ASS1 expression identifying the Philadelphia chromosome-positive (Ph+) ALL subgroup as a stereotypical arginine auxotroph within molecularly diverse B-ALL. Functionally, arginine deprivation with pegargiminase induced robust apoptosis in both Ph+ ALL cell lines and primary samples in an ASS1 dependant manner and was highly effective as a monotherapy treatment in independent Ph+ ALL patient derived xenografts. Mechanistically, arginine deprivation induces endoplasmic reticulum stress mediated apoptosis which was orthogonal to tyrosine kinase inhibition (TKI) mediated outcomes. Using in vitro and in vivo models of non-genetically mediated TKI-resistance, we demonstrate pegargiminase and TKI combinations robustly eradicates TKI resistant leukaemia. Thus, we establish ASS1 deficiency (ASS1-low) as a therapeutically actionable vulnerability in Ph+ ALL and a strategy to bypass TKI-resistance, supporting clinical evaluation of arginine deprivation as a novel adjunct to chemotherapy-free treatment.

This dataset

Open GSE330924 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 GSE330924_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 PRJNA1466188 and SRA study SRP700493. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × TOM-1, Control, vs 3 × TOM-1, ADI-PEG20, vs 3 × RS4;11, Control, vs 3 × RS4;11, ADI-PEG20,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9735811 TOM-1, Control, 3 TOM-1, Control,
GSM9735812 TOM-1, ADI-PEG20, 1 TOM-1, ADI-PEG20,
GSM9735813 TOM-1, ADI-PEG20, 2 TOM-1, ADI-PEG20,
GSM9735814 TOM-1, ADI-PEG20, 3 TOM-1, ADI-PEG20,
GSM9735815 RS4;11, Control, 1 RS4;11, Control,
GSM9735816 RS4;11, ADI-PEG20, 1 RS4;11, ADI-PEG20,
GSM9735817 RS4;11, Control, 2 RS4;11, Control,
GSM9735818 RS4;11, Control, 3 RS4;11, Control,
GSM9735819 RS4;11, ADI-PEG20, 2 RS4;11, ADI-PEG20,
GSM9735820 RS4;11, ADI-PEG20, 3 RS4;11, ADI-PEG20,
GSM9735821 TOM-1, Control, 1 TOM-1, Control,
GSM9735822 TOM-1, Control, 2 TOM-1, Control,

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