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Targeting signaling rewiring and resistant subpopulations in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia [scRNA-seq]

GSE263707 Homo sapiens (human) Single-cell RNA-seq 14 samples Submitted 2025/01/09 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 14 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Homo sapiens (human)
Samples: 14 samples: 6 conditions, mostly in duplicateGroups 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: Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemiaBlood · 2025

Summary (written by the submitters)

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a common high-risk leukemia subtype defined by a kinase-activated gene expression pattern and chemoresistance, with low overall survival rates in both children and adults. Clinical responses of patients with Ph-like ALL to tyrosine kinase inhibitor (TKI)-based therapies are incomplete, suggesting partial oncogene addiction and highlighting the need to elucidate alternative biologic dependencies to cure patients.

Read the full summary ↓

Herein, we report integrated bulk and single-cell multiomics studies of Ph-like ALL cells treated in vitro and in vivo with targeted agents to comprehensively define signaling adaptations and resistant subpopulations. Characterizing residual/resistant human ALL cells harvested from murine spleens revealed transcriptional regulatory network changes and kinase signaling adaptations. We identified key transcription factors including c-MYC and AP1 that mediate transcriptional rewiring associated with therapeutic escape, and demonstrate a specific MYC dependency in Ph-like ALL cells. We found a sub-population of leukemia blasts that have high senescence-associated stem cell-like features that is effectively eradicated only with combined STAT and BCL-2 inhibition. This is clinically significant since both conventional chemotherapy and ruxolitinib are ineffective against senescent stem-like blasts, which may mediate therapeutic tolerance and repopulate relapse. Our findings demonstrate that systems level discovery of key oncogenic dependencies and escape pathways can be exploited for co-targeting or sequential treatment to optimally eradicate blasts and cure this high-risk leukemia subtype.

Published in

Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemia

Ding YY, Sussman JH, Madden K et al. · Blood 2025 · PMID 39774844 · doi:10.1182/blood.2024026482

This dataset

Open GSE263707 in finder → Find more human RNA-seq 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 GSE263707_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1098760 and SRA study SRP500828. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39774844) ↗

Study design

6 conditions, mostly in duplicate

ALL4364_GEX_Day ×2 ALL4364_HTO_Day ×2 JH331_GEX_Day ×2 JH331_HTO_Day ×2 NH011_GEX_Day ×2 NH011_HTO_Day ×2 ALL2128_GEX_Day ×1 ALL2128_HTO_Day ×1

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 14 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

GSM8196835 ALL2128_GEX_Day28
GSM8196836 ALL2128_HTO_Day28
GSM8196837 ALL4364_GEX_Day28 ALL4364_GEX_Day
GSM8196838 ALL4364_GEX_Day3 ALL4364_GEX_Day
GSM8196839 ALL4364_HTO_Day28 ALL4364_HTO_Day
GSM8196840 ALL4364_HTO_Day3 ALL4364_HTO_Day
GSM8196841 JH331_GEX_Day28 JH331_GEX_Day
GSM8196842 JH331_GEX_Day3 JH331_GEX_Day
GSM8196843 JH331_HTO_Day28 JH331_HTO_Day
GSM8196844 JH331_HTO_Day3 JH331_HTO_Day
GSM8196845 NH011_GEX_Day28 NH011_GEX_Day
GSM8196846 NH011_GEX_Day3 NH011_GEX_Day
GSM8196847 NH011_HTO_Day28 NH011_HTO_Day
GSM8196848 NH011_HTO_Day3 NH011_HTO_Day

Datasets on a similar topic

GSE263709 Targeting signaling rewiring and resistant subpopulations in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia [Bulk RNA-seq] 39 samples shares chromosome-like, subpopulations, lymphoblastic, philadelphia, targeting, resistant, rewiring
GSE263710 Targeting signaling rewiring and resistant subpopulations in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia [Bulk ATAC-seq] 39 samples shares chromosome-like, subpopulations, lymphoblastic, philadelphia, targeting, resistant, rewiring
GSE263708 Targeting signaling rewiring and resistant subpopulations in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia [scATAC-seq] 28 samples shares chromosome-like, subpopulations, lymphoblastic, philadelphia, targeting, resistant, rewiring
GSE245284 Venetoclax Resistant Acute Lymphoblastic Leukemia is characterized by Increased Mitochondrial Activity and Can Be Overcome by Co-targeting Oxidative Phosphorylation 10 samples shares lymphoblastic, targeting, resistant
GSE225331 Profiling cancer cells during early metastasis identifies targetable subpopulations [cell line scRNA-seq] 1238 samples shares subpopulations, scrna-seq
GSE330924 ASS1 deficiency defines a therapeutic vulnerability in Philadelphia chromosome-positive acute lymphoblastic leukaemia 12 samples shares lymphoblastic, philadelphia
GSE296685 Targeting HDAC8 sensitizes tyrosine kinase inhibitors in the elimination of B-cell acute lymphoblastic leukemia cells through degradation of HIF-1α 9 samples shares lymphoblastic, targeting
GSE300110 Targeting Menin in T-Lineage Acute Lymphoblastic Leukemia [MEF2COE] 6 samples shares lymphoblastic, targeting

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