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Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation [RNA-Seq]

GSE270550 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 75 samples Submitted 2025/03/11 Platform GPL34290Platform GPL34284Platform GPL28457
Summary
The CEBPA transcription factor is frequently mutated in acute myeloid leukemia (AML). Mutations in the CEBPA gene, which are typically biallelic, result in the production of a shorter isoform known as p30. Both the canonical 42-kDa isoform (p42) and the AML-associated p30 isoform bind chromatin and activate transcription, but the specific transcriptional programs controlled by each protein and how they are linked to a selective advantage in AML is not well understood. Here, we show that cells expressing the AML-associated p30 have reduced baseline inflammatory gene expression and display altered dynamics of transcriptional induction in response to LPS, consequently impacting cytokine secretion. This confers p30-expressing cells an increased resistance to the adverse effects of prolonged exposure to inflammatory signals. Mechanistically, we show that these differences primarily result from the differential regulation of AP-1 family proteins. In addition, we find that the altered function of the AP-1 member ATF4 in p30-expressing cells alters their response to ER stress. Collectively, these findings uncover a novel link between mutant CEBPA, inflammation and the stress response, potentially revealing a new vulnerability in AML.
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Direct links to NCBI, no account and no request form: the whole study as GSE270550_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 75 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1127485 and SRA study SRP515870. Searching any of these in the dataset finder brings you back here.

Study design
13 conditions, mostly in triplicate
Macroph, WT, UT, ×3 Macroph, WT, 2h, ×3 Macroph, WT, 8h, ×3 Macroph, p30, UT, ×3 Macroph, p30, 2h, ×3 Macroph, p30, 8h, ×3 Prog, WT, UT, ×3 Prog, p30, UT, ×3 +6 more

Supports a between-group comparison across 39 samples.

13 replicated groups read from the first 40 of 75 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.

Samples in this study

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