ArticleBlood2018
LSD1 inhibition exerts its antileukemic effect by recommissioning PU.1- and C/EBPα-dependent enhancers in AML.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 115 citations in OpenAlex.
- Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN.Leukemia · 2025Article
- Lysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation.Cell death & disease · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- Covalent adduct Grob fragmentation underlies LSD1 demethylase-specific inhibitor mechanism of action and resistance.Nature communications · 2025Article
- Review
- Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.Developmental cell · 2024Article
- SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3β Signaling Pathway.Chinese journal of integrative medicine · 2024Article
- An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.Molecular cell · 2024Article
- RNA mGenes & diseases · 2024Article
- A guide to epigenetics in leukaemia stem cells.Molecular oncology · 2023Review
- Homodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation.Nature communications · 2023Article
- LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function.JCI insight · 2023Article
- Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia.Molecular cancer research : MCR · 2023Article
- Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine-specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML. We performed a comparative assessment of chromatin dynamics during the treatment of mixed lineage leukemia (MLL)-AF9-driven murine leukemias and MLL-rearranged patient-derived xenografts using 2 distinct but effective differentiation-inducing targeted epigenetic therapies, the LSD1 inhibitor GSK-LSD1 and the DOT1L inhibitor EPZ4777. Intriguingly, GSK-LSD1 treatment caused global gains in chromatin accessibility, whereas treatment with EPZ4777 caused global losses in accessibility. We captured PU.1 and C/EBPα motif signatures at LSD1 inhibitor-induced dynamic sites and chromatin immunoprecipitation coupled with high-throughput sequencing revealed co-occupancy of these myeloid transcription factors at these sites. Functionally, we confirmed that diminished expression of PU.1 or genetic deletion of C/EBPα in MLL-AF9 cells generates resistance of these leukemias to LSD1 inhibition. These findings reveal that pharmacologic inhibition of LSD1 represents a unique path to overcome the differentiation block in AML for therapeutic benefit.
Indexed as
Identifiers
What OpenQuestion holds
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.