GEO series
T-cell dysfunction during blinatumomab therapy in pediatric acute lymphoblastic leukemia
GSE294241
Homo sapiens (human)
RNA-seq (gene expression)
33 samples
Submitted 2025/04/17
Platform GPL34284
At a glance
RNA-seq (gene expression) · human · 33 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
- 33 samples: 11 conditions, mostly in triplicateGroups 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
- T-cell dysfunction during blinatumomab therapy in pediatric acute lymphoblastic leukemiaBlood advances · 2025
Summary (written by the submitters)
Despite the high response rate to the T-cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), maintaining persistent efficacy is a challenge. Limited data from adults with relapsed B-ALL and high disease burden suggest T-cell dysfunction with continuous blinatumomab treatment contributes to loss of response; T-cell function in patients with low disease burden or pediatric B-ALL are uncharacterized.
Read the full summary ↓
Given the recent adoption of blinatumomab in frontline post-remission pediatric B-ALL therapy and the existence of age and leukemia burden-related immune differences, a comprehensive assessment of T-cells is needed to inform optimal continuous treatment duration. Hence, we assessed T-cell function and phenotype during a 28-day continuous intravenous blinatumomab cycle in a pediatric leukemia cohort of 11 patients aged 1-21 years; 8 received blinatumomab in minimal residual disease-negative first remission. By day 14, T-cells exhibited impairments in cytotoxicity (baseline, day 14, day 28 = 72%, 56%, 54%; p = 0.008), IFN-γ production (p = 0.0004), and T-cell receptor (TCR) signaling (mTOR and MEK) that persisted through day 28. The frequency of stem cell memory T-cells declined (p = 0.0004) while those of terminally differentiated (p = 0.012) and TIM3+ (p < 0.0001) cells were elevated at day 14. T-cells at day 14 were marked by exhaustion and terminal differentiation transcriptional signatures; genes encoding inhibitory receptors and negative regulators of TCR signaling were upregulated. Overall, multimodal T-cell dysfunction occurs by day 14. These findings could inform studies to optimize cycle duration and reveal candidate targets for functional studies aimed at ameliorating T-cell dysfunction.
Published in
Ma J, Luong A, Doan A et al.
· Blood advances 2025
· PMID 40267221
· doi:10.1182/bloodadvances.2025015894
This dataset
Open GSE294241 in finder →
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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.
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 GSE294241_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: 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 PRJNA1248854 and SRA study SRP577662. Searching any of these in the dataset finder brings you back here.
Study design
11 conditions, mostly in triplicate
T-cells, patient9, day ×3
T-cells, patient5, day ×3
T-cells, patient11, day ×3
T-cells, patient7, day ×3
T-cells, patient4, day ×3
T-cells, patient6, day ×3
T-cells, patient8, day ×3
T-cells, patient3, day ×3
+3 more
Supports a between-group comparison across 33 samples.
How we read this: 11 replicated groups read from 33 sample titles; they account for 33 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
- GSM8900819 T-cells, patient9, day0 T-cells, patient9, day
- GSM8900820 T-cells, patient9, day14 T-cells, patient9, day
- GSM8900821 T-cells, patient9, day28 T-cells, patient9, day
- GSM8900822 T-cells, patient5, day0 T-cells, patient5, day
- GSM8900823 T-cells, patient5, day14 T-cells, patient5, day
- GSM8900824 T-cells, patient5, day28 T-cells, patient5, day
- GSM8900825 T-cells, patient11, day0 T-cells, patient11, day
- GSM8900826 T-cells, patient11, day14 T-cells, patient11, day
- GSM8900827 T-cells, patient11, day28 T-cells, patient11, day
- GSM8900828 T-cells, patient7, day0 T-cells, patient7, day
- GSM8900829 T-cells, patient7, day14 T-cells, patient7, day
- GSM8900830 T-cells, patient7, day28 T-cells, patient7, day
- GSM8900831 T-cells, patient4, day0 T-cells, patient4, day
- GSM8900832 T-cells, patient4, day14 T-cells, patient4, day
- GSM8900833 T-cells, patient4, day28 T-cells, patient4, day
- GSM8900834 T-cells, patient6, day0 T-cells, patient6, day
- GSM8900835 T-cells, patient6, day14 T-cells, patient6, day
- GSM8900836 T-cells, patient6, day28 T-cells, patient6, day
- GSM8900837 T-cells, patient8, day0 T-cells, patient8, day
- GSM8900838 T-cells, patient8, day14 T-cells, patient8, day
- GSM8900839 T-cells, patient8, day28 T-cells, patient8, day
- GSM8900840 T-cells, patient3, day0 T-cells, patient3, day
- GSM8900841 T-cells, patient3, day14 T-cells, patient3, day
- GSM8900842 T-cells, patient3, day28 T-cells, patient3, day
- GSM8900843 T-cells, patient2, day0 T-cells, patient2, day
- GSM8900844 T-cells, patient2, day14 T-cells, patient2, day
- GSM8900845 T-cells, patient2, day28 T-cells, patient2, day
- GSM8900846 T-cells, patient1, day0 T-cells, patient1, day
- GSM8900847 T-cells, patient1, day14 T-cells, patient1, day
- GSM8900848 T-cells, patient1, day28 T-cells, patient1, day
- GSM8900849 T-cells, patient10, day0 T-cells, patient10, day
- GSM8900850 T-cells, patient10, day14 T-cells, patient10, day
- GSM8900851 T-cells, patient10, day28 T-cells, patient10, day
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