Omics · study · 2026
IKZF2 is downregulated in the presence of TLX3 and mutant IL7R: a novel axis of transcriptional dysregulation in leukemia
Listed in NCBI GEO
Current treatment protocols for acute lymphoblastic leukemia (ALL), while generally successful, are hampered by significant short-term and long-term side effects.
Description
Furthermore, patients with relapsed or refractory disease have limited treatment options and poor prognosis. Therefore, a better understanding of the genetic alterations contributing to leukemogenesis is needed to develop novel, targeted therapies that are safe and effective.
While oncogenic mutations of IL7R (mutIL7R) have been identified in both T-ALL and B-ALL cases, we previously demonstrated mutIL7R alone was insufficient to cause leukemia, suggesting the presence of cooperating genetic lesions. Consistent with this hypothesis, we now report mice transplanted with T cells overexpressing TLX3, a homeobox transcription factor frequently activated in T-ALL, in combination with mutIL7R develop an aggressive, mixed lineage leukemia.
Read the rest (1 more)
Using a comprehensive approach of scRNA-seq, immunophenotyping, and TCRβ sequencing, we found that TLX3 downregulated Helios (IKZF2) and enhanced proliferative signaling via the PI3K/AKT pathway. Our findings uncover the cooperative oncogenic potential of mutIL7R and TLX3 in driving mixed lineage leukemia and emphasize the importance of the PI3K/AKT pathway in this process. Additionally, these findings suggest that PI3K inhibitors could be a promising therapeutic strategy for leukemias harboring these mutations.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298907 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298907 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1271774 ncbi.nlm.nih.gov/bioproject/PRJNA1271774 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus · Other
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · Sequencing 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE298907 | 13 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[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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 (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 |