Omics · study · 2026
Casein kinase 1δ/ε inhibition suppresses CLL through cell-intrinsic and microenvironmental mechanisms
Listed in NCBI GEO
Chronic lymphocytic leukemia (CLL) is a consequence of pathological B cell accumulation in blood and lymphoid organs.
Description
Due to high refractoriness, CLL is considered incurable which calls for novel therapeutic options. Previously, we showed casein kinase 1δ/ε (CK1δ/ε) inhibition prolonged survival of Eµ-TCL1 mice with CLL-like disease.
Herein, we elucidate mechanisms mediating CK1δ/ε inhibition efficacy in CLL suppression. Using in vivo Eµ-TCL1 adoptive transfer (AT) model, we showed CK1δ/ε inhibition mediated cell cycle slowdown and CLL cell accumulation at S/G2 interface. This observation was validated using multiple CLL cell lines and EdU/Click-iT reaction applied in vivo.
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Furthermore, we showed CK1δ/ε inhibition led to T cell decrease in lymph nodes (LN). Using system mimicking LN microenvironment in vitro, we observed CK1δ/ε inhibition triggered downregulation of nuclear factor κ B (NFκB) pathway that acts downstream of T-cell-mediated CD40L:CD40 stimulus, inducing CLL cell proliferation. Finally, we showed CK1δ/ε inhibition counteracted proliferation of CLL cells from wide range of patients, with lower efficacy only in patients bearing TP53 defects.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304722 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304722 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1302404 ncbi.nlm.nih.gov/bioproject/PRJNA1302404 ↗
project · from NCBI GEO
- PubMed 41939248 pubmed.ncbi.nlm.nih.gov/41939248 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE304722 | 15 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].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[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 |