ArticleHaematologica2013
The trithorax protein partner menin acts in tandem with EZH2 to suppress C/EBPα and differentiation in MLL-AF9 leukemia.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Menin in Cancer.Genes · 2024Review
- Review
- Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023Article
- Menin Enhances Androgen Receptor-Independent Proliferation and Migration of Prostate Cancer Cells.Molecules and cells · 2022Article
- A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- JAM-A Acts via C/EBP-α to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function.Circulation research · 2020Article
- Disruption of the menin-MLL interaction triggers menin protein degradation via ubiquitin-proteasome pathway.American journal of cancer research · 2019Article
- TRIB2 regulates the differentiation of MLL-TET1 transduced myeloid progenitor cells.Journal of molecular medicine (Berlin, Germany) · 2018Article
- MENIN loss as a tissue-specific driver of tumorigenesis.Molecular and cellular endocrinology · 2018Review
- A Review of the Scaffold Protein Menin and its Role in Hepatobiliary Pathology.Gene expression · 2017Review
- Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase.International journal of molecular sciences · 2017Article
- Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity.Nucleus (Austin, Tex.) · 2016Review
- Targeting EZH2 and PRC2 dependence as novel anticancer therapy.Experimental hematology · 2015Review
- Review
- Review
- Menin is required for optimal processing of the microRNA let-7a.The Journal of biological chemistry · 2014Article
- Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Trithorax and polycomb group proteins antagonistically regulate the transcription of many genes, and cancer can result from the disruption of this regulation. Deregulation of trithorax function occurs through chromosomal translocations involving the trithorax gene MLL, leading to the expression of MLL fusion proteins and acute leukemia. It is poorly understood how MLL fusion proteins block differentiation, a hallmark of leukemogenesis. We analyzed the effect of acute depletion of menin, a close partner of MLL that is critical for MLL and MLL-AF9 recruitment to target genes, on MLL-AF9 leukemia cell differentiation using an in vivo model. We performed cDNA microarray analysis of menin-regulated genes from primary leukemia cells to determine menin-regulated pathways involved in suppressing MLL-AF9 leukemia cell differentiation. We found that menin binds the promoter of the polycomb gene Ezh2, and promotes its expression. EZH2 interacts with the differentiation-promoting transcription factor C/EBPα and represses C/EBPα target genes. Menin depletion reduces MLL binding to the Ezh2 locus, EZH2 expression, and EZH2 binding and repressive H3K27 methylation at C/EBPα target genes, thereby inducing the expression of pro-differentiation C/EBPα targets. In conclusion, our results show that in contrast to its classical role antagonizing trithorax function, the polycomb group protein EZH2 collaborates with trithorax-associated menin to block MLL-AF9 leukemia cell differentiation, uncovering a novel mechanism for suppression of C/EBPα and leukemia cell differentiation, through menin-mediated upregulation of EZH2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.