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Type 2 calreticulin mutations activate ATF6 to promote BCL-xL-mediated survival in myeloproliferative neoplasms

GSE288386 Homo sapiens (human) RNA-seq (gene expression) 37 samples Submitted 2025/05/31 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 37 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
Myeloproliferative neoplasmsThis series is part of our curated briefing on it.
Samples
37 samples: 6 conditions, mostly with about 5 replicates eachGroups 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
Type 2 calreticulin mutations activate ATF6 to promote BCL-xL-mediated survival in myeloproliferative neoplasmsBlood · 2025
Summary (written by the submitters)
The majority of calreticulin (CALR) mutations in myeloproliferative neoplasms (MPNs) are classified as either type 1, a 52 base-pair deletion (CALRdel52), or type 2, a 5 base-pair insertion (CALRins5). Both are gain-of-function (GOF) mutations that generate an identical mutant C-terminal tail, which mediates the binding to and activation of the thrombopoietin receptor MPL.
Read the full summary ↓
We recently reported that despite this shared GOF, CALRdel52 but not CALRins5 mutations cause loss of calcium binding function, leading to activation of and dependency on the IRE1a/XBP1 pathway of the unfolded protein response (UPR). This led us to ask whether CALRins5 mutations activate and depend on a different UPR pathway, and whether this is likewise mediated by a mutation type-specific loss-of- function (LOF). Here, we show that CALRins5 mutations lead to activation of the ATF6 pathway of the UPR due to loss of CALR chaperone function. This LOF is caused by interference of the CALRins5 mutant C-terminus with key chaperone residue H170. Further, we show that CALRins5 cells are partially dependent on ATF6 for cytokine-independent growth, and identify BCL-xL as a transcriptional target of ATF6 that promotes type 2 CALR mutant cell survival.
Published in
Type 2 calreticulin mutations activate ATF6 to promote BCL-xL-mediated survival in myeloproliferative neoplasms
Arellano NS, Heaton WL, Nauman MC et al. · Blood 2025 · PMID 40403318 · doi:10.1182/blood.2024026940
This dataset
Open GSE288386 in finder → Find more human RNA-seq datasets → Myeloproliferative neoplasms 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 GSE288386_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 PRJNA1217339 and SRA study SRP560702. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40403318) ↗
Study design
6 conditions, mostly with about 5 replicates each
Type 2 ET ×8 Type 1 ET ×5 Type 1 PMF ×5 JAK2 ET ×5 JAK2 PMF ×5 Type 2 PMF ×2 Healthy Control B ×1 Healthy Control S ×1 +5 more

Supports a between-group comparison across 30 samples.

How we read this: 6 replicated groups read from 37 sample titles; they account for 30 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
More Myeloproliferative neoplasms datasets

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