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NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma [RNA-seq]

GSE328216 Homo sapiens (human) Single-cell RNA-seq 24 samples Submitted 2026/07/15 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 24 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
24 samples: 12 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
NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple MyelomaBlood · 2026
Summary (written by the submitters)
The t(4;14) chromosomal translocation drives overexpression of the histone methyltransferase NSD2 and defines a high-risk segment of multiple myeloma (MM) patients. Herein, we report the discovery of NSD2-LDD, a cereblon-recruiting and PWWP1-mediated ligand directed degrader (LDD) that selectively and potently eliminates full length and PWWP1 domain containing NSD2 protein.
Read the full summary ↓
NSD2-LDD treatment induces global loss of H3K36me2 leading to promoter-proximal spreading of H3K27me3 and re-wiring of cis-regulatory interactions that reverse t(4;14) transcriptional programs. These effects suppress MM disease-associated phenotypes including stromal adhesion, three-dimensional colony growth and paracrine signaling. By integrating patient single cell profiles with model 3D epigenomic and spatial transcriptomics, we delineate t(4;14) disease state and the tumor-intrinsic reprogramming and resultant remodeling of the bone marrow microenvironment upon NSD2 degradation. In cell line derived xenografts and genetically engineered mouse models of t(4;14), NSD2-LDD extends median survival accompanied by tumoral H3K36me2 loss and niche re-modelling. Collectively, this work validates NSD2 as a tractable dependency and supports clinical development of NSD2 degradation as a novel, targeted therapeutic strategy in high-risk MM.
Published in
NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma
Hu B, Edwards J, Modi H et al. · Blood 2026 · PMID 42371798 · doi:10.1182/blood.2025031998
This dataset
Open GSE328216 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 GSE328216_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 PRJNA1454372 and SRA study SRP692379. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42371798) ↗
Study design
12 conditions, mostly in duplicate
KMS-11-100nM-Day14 ×2 KMS-11-100nM-Day7 ×2 KMS-11-1uM-Day14 ×2 KMS-11-1uM-Day7 ×2 KMS-11-DMSO-Day14 ×2 KMS-11-DMSO-Day7 ×2 KMS-34-100nM-Day14 ×2 KMS-34-100nM-Day7 ×2 +4 more

Supports a between-group comparison across 24 samples.

How we read this: 12 replicated groups read from 24 sample titles; they account for 24 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
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