ArticleMolecular cell2022
MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 68 citations in OpenAlex.
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- Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines.International journal of molecular sciences · 2026Article
- Chromosomal rearrangement-enhanced mRNA stability drives the oncogenic potential of fusion genes in pediatric leukemia.Haematologica · 2026Article
- Comprehensive lincRNA Transcriptome in Acute Myeloid Leukemia: Integrating Known and Newly Identified lincRNAs Across Pediatric and Adult Cohorts.Non-coding RNA · 2026Article
- Cell type-specific spatiotemporal control of GFP-tagged protein degradation in mice.The Journal of cell biology · 2026Article
- Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.The FEBS journal · 2026Review
- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- chromIDEAS reveals epigenetic dynamics via multi-dimensional clustering of chromatin states.Nucleic acids research · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis.Nature communications · 2026Article
- Matrine enhances RLS3-induced ferroptosis at non-toxic doses in acute myeloid leukemia cells with MLL rearrangement.American journal of cancer research · 2026Article
- Histone methyltransferase DOT1L maintains cell state and restricts cytotoxic potential of CD8 T cells.Science advances · 2025Article
- Catalytic Inhibition of KAT6/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia.Cancer discovery · 2025Article
- Phenotypic screening converges on CDK9 inhibition as a therapeutic strategy in translocation renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer.Cell reports. Medicine · 2025Article
- Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.Haematologica · 2025Article
- Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12.Nature communications · 2025Article
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
MLL rearrangements produce fusion oncoproteins that drive leukemia development, but the direct effects of MLL-fusion inactivation remain poorly defined. We designed models with degradable MLL::AF9 where treatment with small molecules induces rapid degradation. We leveraged the kinetics of this system to identify a core subset of MLL::AF9 target genes where MLL::AF9 degradation induces changes in transcriptional elongation within 15 minutes. MLL::AF9 degradation subsequently causes loss of a transcriptionally active chromatin landscape. We used this insight to assess the effectiveness of small molecules that target members of the MLL::AF9 multiprotein complex, specifically DOT1L and MENIN. Combined DOT1L/MENIN inhibition resembles MLL::AF9 degradation, whereas single-agent treatment has more modest effects on MLL::AF9 occupancy and gene expression. Our data show that MLL::AF9 degradation leads to decreases in transcriptional elongation prior to changes in chromatin landscape at select loci and that combined inhibition of chromatin complexes releases the MLL::AF9 oncoprotein from chromatin globally.
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