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Longitudinal omics data followed by preclinical treatment studies identify proteasome inhibition as potential salvage strategy for ibrutinib-resistant CLL

GSE215414 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2024/10/29 Platform GPL21103
At a glance

RNA-seq (gene expression) · mouse · 15 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
Mus musculus (mouse)
Samples
15 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.
Paper
Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLLNature communications · 2025
Summary (written by the submitters)
Chronic lymphocytic leukemia (CLL) is a malignant lymphoproliferative disorder characterized by the accumulation of small mature B cells in blood and secondary lymphoid tissues. Novel drugs, such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, have greatly improved survival expectations of CLL patients, nevertheless acquired drug resistance represents a major challenge and the complete molecular mechanisms of which have not been elucidated yet.
Read the full summary ↓
In order to fill this knowledge gap, we generated a mouse model of ibrutinib resistance by treating mice upon adoptive transfer of Eµ-TCL1 leukemia (TCL1-CLL) continuously with ibrutinib. After an initial response to the treatment, relapse under therapy occurs with an aggressive outgrowth of the malignant cells, resembling observations in patients. To unravel relapse mechanism, we performed transcriptome and proteome analyses of sorted TCL1-CLL cells both during treatment and after relapse. Comparative analysis of these omics layers suggested alterations in the proteasome activity as a driver of ibrutinib resistance. Accordingly, we showed that preclinical treatment with the irreversible proteasome inhibitor (PI) carfilzomib administered upon ibrutinib resistance prolonged survival of mice, thus acting as salvage therapy. Longitudinal proteomic analysis of CLL patients with ibrutinib resistance identified deregulation in protein post-translational modifications. In addition, CLL cells from ibrutinib-resistant patients effectively responded to several PIs in co-culture assays. Altogether, our results from orthogonal omics approaches identified proteasome inhibition as potentially attractive innovative salvage treatment option for CLL patients resistant or refractory to ibrutinib.
Published in
Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL
Arseni L, Sigismondo G, Yazdanparast H et al. · Nature communications 2025 · PMID 39863584 · doi:10.1038/s41467-025-56318-7
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 GSE215414_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 PRJNA890232 and SRA study SRP402418. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 15 more — browse all 15 samples with per-sample file links →

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