Omics · study · 2026
Latexin deletion in the bone marrow niche suppresses leukemia via LIFR signaling downregulation and immune activation
Listed in NCBI GEO
Acute myeloid leukemia (AML) is the most common adult leukemia diagnosis.
Description
Bone marrow (BM) niche significantly influences the initiation and progression of AML. However, our knowledge about the impact of leukemic niche on leukemia stem cells (LSC) and leukemogenesis is still limited.
In this study, we identified a novel function of latexin (Lxn) in the cell-extrinsic regulation of leukemogenesis. Using a MLL-AF9-induced AML mouse model in wild-type (WT) and Lxn knockout (Lxn-/-) recipient mice, we found that Lxn deletion in the BM niche enhances the survival of AML mice by suppressing LSCs and reducing blood blasts. Single-cell RNA sequencing of stromal cells and cell communication analysis uncovered downregulation of the leukemia inhibitory factor receptor (LIFR) signaling pathway in the Lxn-/- niche, particularly within mesenchymal stromal cells (MSCs).
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Mechanistically, reduced LIFR level in Lxn-/- MSCs upregulates Cxcl9 expression, leading to increased recruitment of CD8 T cells and enhanced cytotoxicity against leukemic cells. Combination of Lxn niche deletion and immune checkpoint inhibitor PD-L1 further prolonged survival. The findings have important clinical implications, suggesting that Lxn inhibition could improve the efficacy of AML therapies by targeting the leukemia niche and enhancing immune surveillance.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330528 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330528 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1463322 ncbi.nlm.nih.gov/bioproject/PRJNA1463322 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE330528 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |