ArticleLeukemia2019
CEBPA-mutated leukemia is sensitive to genetic and pharmacological targeting of the MLL1 complex.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
- The prognostic impact of CEBPA mutation in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2026Article
- Ziftomenib with venetoclax and azacitidine for relapsed/refractory NPM1-mutated acute myeloid leukemia.Blood · 2026Article
- The new era of AML therapy: current standards and emerging targets.International journal of clinical oncology · 2026Review
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- 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
- Review
- Arginine methylation of the p30 C/EBPα oncoprotein regulates progenitor proliferation and myeloid differentiation.iScience · 2024Article
- CEBPA mutations in acute myeloid leukemia: implications in risk stratification and treatment.International journal of hematology · 2024Review
- The adsorption of drugs on nanoplastics has severe biological impact.Scientific reports · 2024Article
- Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.European journal of medical genetics · 2023Review
- TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression.Nature communications · 2023Article
- Arrayed CRISPR/Cas9 Screening for the Functional Validation of Cancer Genetic Dependencies.Bio-protocol · 2022Article
- Comprehensive assessment of differential ChIP-seq tools guides optimal algorithm selection.Genome biology · 2022Article
- Straight to the Point-The Novel Strategies to Cure Pediatric AML.International journal of molecular sciences · 2022Review
- Article
- Acute Myeloid Leukemia WithFrontiers in oncology · 2022Review
- Review
- Identification of gene targets of mutant C/EBPα reveals a critical role for MSI2 in CEBPA-mutated AML.Leukemia · 2021Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
Abstract
The gene encoding the transcription factor C/EBPα is mutated in 10-15% of acute myeloid leukemia (AML) patients. N-terminal CEBPA mutations cause ablation of full-length C/EBPα without affecting the expression of a shorter oncogenic isoform, termed p30. The mechanistic basis of p30-induced leukemogenesis is incompletely understood. Here, we demonstrate that the MLL1 histone-methyltransferase complex represents a critical actionable vulnerability in CEBPA-mutated AML. Oncogenic C/EBPα p30 and MLL1 show global co-localization on chromatin and p30 exhibits robust physical interaction with the MLL1 complex. CRISPR/Cas9-mediated mutagenesis of MLL1 results in proliferation arrest and myeloid differentiation in C/EBPα p30-expressing cells. In line, CEBPA-mutated hematopoietic progenitor cells are hypersensitive to pharmacological targeting of the MLL1 complex. Inhibitor treatment impairs proliferation and restores myeloid differentiation potential in mouse and human AML cells with CEBPA mutations. Finally, we identify the transcription factor GATA2 as a direct critical target of the p30-MLL1 interaction. Altogether, we show that C/EBPα p30 requires the MLL1 complex to regulate oncogenic gene expression and that CEBPA-mutated AML is hypersensitive to perturbation of the MLL1 complex. These findings identify the MLL1 complex as a potential therapeutic target in AML with CEBPA mutations.
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Registered trials
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.