Omics · study · 2026
KLF4/MLL3 Complex axis Drives NRBP2 Transcription to Eliminate Acute Myeloid Leukemia Cells [Cut & Tag]
Listed in NCBI GEO
Acute myeloid leukemia (AML) is a heterogeneous malignancy rooted in hematopoietic stem cell dysregulation.
Description
Despite therapeutic advances, clinical outcomes remain unsatisfactory. Here, we identify KLF4, a zinc-finger (ZnF) transcription factor with previously reported context-dependent roles in hematologic malignancies, as a negative regulator of AML proliferation.
Mechanistically, KLF4 interacts with the MLL3 histone methyltransferase complex, comprising MLL3, WDR5, RBBP5 and ASH2L. KLF4 engages the catalytic subunit MLL3 and the allosteric regulator ASH2L through its ZnF and transrepression (TRD) domains, thereby activating transcription of the tumor suppressor gene NRBP2. Furthermore, integrated transcriptional analysis revealed TNIK as a convergent effector of the KLF4–NRBP2 tumor-suppressive circuit in acute myeloid leukemia.
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Pharmacological blockade of TNIK with the selective small-molecule inhibitor TNIK-IN-1 selectively impaired leukemic cell proliferation while sparing normal hematopoiesis. Consequently, our findings reveal a previously unrecognized KLF4–MLL3 complex–NRBP2 transcriptional axis that suppresses AML survival through TNIK, highlighting a potential therapeutic strategy for AML.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328080 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328080 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1453810 ncbi.nlm.nih.gov/bioproject/PRJNA1453810 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE328080 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | 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 |