Omics · study · 2026
Comprehensive Molecular and Functional Analysis of NUTM1-Rearranged Leukemia [methylation array]
Listed in NCBI GEO
NUTM1-rearrangement (NUTM1-r) defines a significant subset of B-cell acute lymphoblastic leukemia (B-ALL), particularly in infants lacking KMT2A-rearrangements (KMT2A-r), yet its underlying molecular characteristics remain poorly understood.
Description
Here, we establish that NUTM1-r leukemia is a discrete entity characterized by a unique transcriptional and epigenetic landscape, notably featuring global DNA hypomethylation, irrespective of the 5' fusion partner.
Functional interrogation of NUTM1 fusions reveals a dual oncogenic role: they drive commitment towards the B-lymphoid lineage while concurrently conferring potent leukemic stem cell properties. Strikingly, expression of a representative fusion, BRD9-NUTM1, is sufficient to induce serially-transplantable prepro-B-like leukemia in vivo, faithfully recapitulating the key molecular and immunophenotypic features of human NUTM1-r B-ALL.
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Mechanistically, NUTM1 fusions establish an aberrant chromatin state, marked by global enhancement of H3K27 acetylation and the creation of distinctive open chromatin regions that co-opt both B-lineage and stemness-related transcriptional programs, including those involving NF-κB and posterior HoxA genes. In stark contrast to resistant KMT2A-r leukemias, NUTM1-r leukemic cells exhibit a profound sensitivity to chemotherapy.
This vulnerability is mechanistically linked to the leukemia's dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, revealing specific vulnerabilities that rationalize their favorable clinical outcomes and suggest opportunities for modified therapeutic strategies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307522 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307522 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1321912 ncbi.nlm.nih.gov/bioproject/PRJNA1321912 ↗
project · from NCBI GEO
- PubMed 41460961 pubmed.ncbi.nlm.nih.gov/41460961 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Methylation profiling by array · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- DNA methylation profiling 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE307522 | 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:methylation-profiling-by-array | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].local:method:dna-methylation-profiling | 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 |