GEO series

Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma

GSE307399 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/09/05 Platform GPL28038

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: Multiple myelomaThis series is part of our curated briefing on it.
Samples: 12 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.

Summary (written by the submitters)

The progression of multiple myeloma (MM), an incurable malignancy of plasma cells, is oftenassociated with the suppression of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. The mechanisms underlying this suppression remain largely unknown. Here, we identified STK17B kinase as a critical suppressor of ferroptosis in MM.

Read the full summary ↓

Elevated levels of STK17B are associated with poor overall survival in MM patients and STK17B expression is significantly higher in relapsed vs newly diagnosed MM cases. We found that inhibiting STK17B in MM cells increased the labile iron pool, enhanced lipid peroxidation, and sensitized cells to conventional anti-MM therapies. Notably, an orally available, in-house-generated STK17B inhibitor induced ferroptosis and significantly reduced tumor growth in MM xenograft mouse models. Mechanistically, proximity labeling assay combined with the phospho-proteomic analysis identified two major regulators of iron uptake and transport as direct targets of STK17B: iron-responsive element binding protein 2 (IREB2) and heat shock protein family B member 1 (HSPB1). We demonstrated that STK17B phosphorylates critical regulatory sites on IREB2 (S157) and HSPB1 (S15), thereby modulating the balance between IREB2 and HSPB1 downstream effectors, pro-ferroptotic transferrin receptor and anti-ferroptotic ferritin heavy chain proteins. Furthermore, we demonstrated that STK17B indirectly maintains activating phosphorylation of STAT3, a ferroptosis suppressor and a major driver of MM pathobiology. Our findings uncovered a clinically relevant and targetable STK17B-pIREB2S157/pHSPB1S15 signaling axis that suppresses ferroptosis and contributes to drug resistance in MM.

This dataset

Open GSE307399 in finder → Find more human RNA-seq datasets → Multiple myeloma 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 GSE307399_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 PRJNA1320666 and SRA study SRP617762. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly in duplicate

KMS11 cells, shControl ×2 KMS11 cells, sh1 STK17B ×2 KMS11 cells, sh2 STK17B ×2 KMS11 cells, STK17B inhibitor ×2 KMS11 cells, Vector ×2 KMS11 cells, STK17B overexpression ×2

Supports a case/control comparison: 2 samples read as cases, 2 as controls.

How we read this: 6 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

GSM9223363 KMS11 cells, shControl REP1 KMS11 cells, shControl
GSM9223364 KMS11 cells, shControl REP2 KMS11 cells, shControl
GSM9223365 KMS11 cells, sh1 STK17B REP1 KMS11 cells, sh1 STK17B
GSM9223366 KMS11 cells, sh1 STK17B REP2 KMS11 cells, sh1 STK17B
GSM9223367 KMS11 cells, sh2 STK17B REP1 KMS11 cells, sh2 STK17B
GSM9223368 KMS11 cells, sh2 STK17B REP2 KMS11 cells, sh2 STK17B
GSM9223369 KMS11 cells, STK17B inhibitor REP1 KMS11 cells, STK17B inh…
GSM9223370 KMS11 cells, STK17B inhibitor REP2 KMS11 cells, STK17B inh…
GSM9223371 KMS11 cells, Vector REP1 KMS11 cells, Vector
GSM9223372 KMS11 cells, Vector REP2 KMS11 cells, Vector
GSM9223373 KMS11 cells, STK17B overexpression REP1 KMS11 cells, STK17B ove…
GSM9223374 KMS11 cells, STK17B overexpression REP2 KMS11 cells, STK17B ove…

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.