ArticleBlood cancer journal2021
Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells.
Article in Blood cancer journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- KIT-dependent acute myeloid leukemias are responsive to LSD1 inhibition.Clinical epigenetics · 2026Article
- Highly effective combination of BRG1/BRM inhibitor with BET inhibitor or decitabine for high-risk MECOM-rearranged AML.HemaSphere · 2026Article
- 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
- Article
- Epigenomic Modulators and Thyroid Hormone Receptor β Agonists: A New Paradigm for Tumor Suppression in Thyroid Cancer.Endocrinology · 2025Review
- SOHO State of the Art Updates and Next Questions | Challenging Scenarios in the Management of Myeloproliferative Neoplasms.Clinical lymphoma, myeloma & leukemia · 2025Review
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.Haematologica · 2025Review
- Functions and mechanisms of non-histone post-translational modifications in cancer progression.Cell death discovery · 2025Review
- Article
- Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.Blood advances · 2024Article
- Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression.Leukemia · 2024Article
- Recent Advances towards the Understanding of Secondary Acute Myeloid Leukemia Progression.Life (Basel, Switzerland) · 2024Review
- Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).Blood cancer journal · 2024Article
- An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.The EMBO journal · 2023Article
- Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia.Molecular cancer research : MCR · 2023Article
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.Blood cancer journal · 2023Article
- LSD1 inhibition modulates transcription factor networks in myeloid malignancies.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 1 country.
Funding
Abstract
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.
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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.