Omics · study · 2026
Phenotypic consequences of constitutively active and nonphosphorylatable mutations of Stat5 in B-ALL cells
Listed in NCBI GEO
While B-ALL cells rely on oncogenic STAT5 signaling, negative feedback regulators of STAT5, such as SOCS2 and CISH, are highly expressed in aggressive B-ALL and their high expression levels are strongly associated with poor clinical outcomes.
Description
Here, we examined the phenotypic consequences of active and inactive states of STAT5 by studying constitutively active (CA) and nonphosphorylatable Y694F (YF) mutations of Stat5 in a murine B-ALL model.
Consistent with the requirement for adaptive STAT5-feedback control, both Stat5-CA(+) and Stat5-YF(+) B-ALL cells were rapidly depleted from the cell culture, likely due to senescence and quiescence, respectively. Induction of Stat5-CA caused biomass accumulation, whereas Stat5-YF induced rapid cell shrinkage, resembling the differentiation from large pre-B to small pre-B cells. An RNA-seq gene expression analysis revealed that Stat5-CA increased the expression levels of Myc in parallel with genes involved in the unfolded protein response (UPR).
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Conversely, Stat5-YF increased the expression levels of Bcl6 and autophagic genes, such as LC3B. In accordance with the gene expression profiles, Stat5-YF increased phosphatidylethanolamine (PtdEtn) content and promoted PtdEtn-LC3B-dependent autophagosome formation. Supplementation of the PtdEtn precursor ethanolamine promoted autophagy and rescued Stat5-CA(+) B-ALL cells from ER stress and cellular senescence.
Our results demonstrate that negative feedback regulators of STAT5, including SOCS2 and CISH, are not only biomarkers of increased oncogenic STAT5 activity and a more aggressive course of disease linked to poor overall outcomes. Importantly, negative STAT5 feedback control mechanisms are essential for enabling nimble adaptations of B-ALL cells in response to fluctuations in oncogenic signaling strength and nutrient availability during distinct metabolic states of cellular activation and quiescence.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290715 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290715 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1229611 ncbi.nlm.nih.gov/bioproject/PRJNA1229611 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 68% · Disease 75% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE290715 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (68%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |