ArticleCell stem cell2022
An oncogenic enhancer encodes selective selenium dependency in AML.
Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Targeting oncogenic FLT3 uncovers a ferroptosis vulnerability through selenocysteine recoding in acute myeloid leukaemia.Nature cell biology · 2026Article
- Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.Cancer research · 2026Article
- METTL5 regulates SEPHS2-mediated selenoprotein synthesis to promote multiple myeloma survival and progression.Cell death & disease · 2025Article
- Selenium compounds for cancer prevention and therapy - human clinical trial considerations.Medical review (2021) · 2025Review
- Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition.Nature communications · 2025Article
- Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A.Journal of cellular physiology · 2025Article
- Target protein identification in live cells and organisms with a non-diffusive proximity tagging system.eLife · 2024Article
- Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.EMBO molecular medicine · 2024Article
- Article
- Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024Review
- A Diet Lacking Selenium, but Not Zinc, Copper or Manganese, Induces Anticancer Activity in Mice with Metastatic Cancers.Nutrients · 2024Article
- Systematic analysis of copper, zinc, and selenium levels in JAK2 V617F-positive myeloproliferative neoplasms.Annals of hematology · 2024Article
- Article
- Selenium and Selenoproteins in Health.Biomolecules · 2023Review
- Therapeutic Benefits of Selenium in Hematological Malignancies.International journal of molecular sciences · 2022Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Deregulation of transcription is a hallmark of acute myeloid leukemia (AML) that drives oncogenic expression programs and presents opportunities for therapeutic targeting. By integrating comprehensive pan-cancer enhancer landscapes with genetic dependency mapping, we find that AML-enriched enhancers encode for more selective tumor dependencies. We hypothesized that this approach could identify actionable dependencies downstream of oncogenic driver events and discovered a MYB-regulated AML-enriched enhancer regulating SEPHS2, a key component of the selenoprotein production pathway. Using a combination of patient samples and mouse models, we show that this enhancer upregulates SEPHS2, promoting selenoprotein production and antioxidant function required for AML survival. SEPHS2 and other selenoprotein pathway genes are required for AML growth in vitro. SEPHS2 knockout and selenium dietary restriction significantly delay leukemogenesis in vivo with little effect on normal hematopoiesis. These data validate the utility of enhancer mapping in target identification and suggest that selenoprotein production is an actionable target in AML.
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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.