ArticleBlood cancer discovery2022
Translational Activation of ATF4 through Mitochondrial Anaplerotic Metabolic Pathways Is Required for DLBCL Growth and Survival.
Article in Blood cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 25 citations in OpenAlex.
- TRIM28 facilitates diffuse large B-cell lymphoma progression by inducing glycolytic reprogramming through the E2F1/PKM2 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Review
- Amino acid-based risk stratification model improves prognostic precision in diffuse large B-cell lymphoma.Cancer cell international · 2025Article
- MiR-204-5p mediates PERK inhibition to suppress growth and induce apoptosis in ovarian cancer through the eIF2α/ATF-4/CHOP pathway.Scientific reports · 2025Article
- A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features.Cancer medicine · 2025Article
- Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.Frontiers in immunology · 2025Review
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- Targeting SIRT3 sensitizes glioblastoma to ferroptosis by promoting mitophagy and inhibiting SLC7A11.Cell death & disease · 2024Article
- Identification of a prognostic signature based on five ferroptosis-related genes for diffuse large B-cell lymphoma.Cancer biomarkers : section A of Disease markers · 2024Article
- Long non-coding RNA mitophagy and ALK-negative anaplastic lymphoma-associated transcript: a novel regulator of mitophagy in T-cell lymphoma.Haematologica · 2023Article
- Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1.Molecular cancer therapeutics · 2023Article
- Simultaneous inhibition of Sirtuin 3 and cholesterol homeostasis targets acute myeloid leukemia stem cells by perturbing fatty acid β-oxidation and inducing lipotoxicity.Haematologica · 2023Article
- Potential Pathogenic Impact of Cow's Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2023Review
- Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies.Frontiers in oncology · 2023Article
- Targeting the integrated stress response in hematologic malignancies.Experimental hematology & oncology · 2022Review
- Transcriptional and metabolic remodeling in clear cell renal cell carcinoma caused by ATF4 activation and the integrated stress response (ISR).Molecular carcinogenesis · 2022Article
- The metabolic plasticity of B cells.Frontiers in molecular biosciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Diffuse large B-cell lymphomas (DLBCL) are broadly dependent on anaplerotic metabolism regulated by mitochondrial SIRT3. Herein we find that translational upregulation of ATF4 is coupled with anaplerotic metabolism in DLBCLs due to nutrient deprivation caused by SIRT3 driving rapid flux of glutamine into the tricarboxylic acid (TCA) cycle. SIRT3 depletion led to ATF4 downregulation and cell death, which was rescued by ectopic ATF4 expression. Mechanistically, ATF4 translation is inhibited in SIRT3-deficient cells due to the increased pools of amino acids derived from compensatory autophagy and decreased glutamine consumption by the TCA cycle. Absence of ATF4 further aggravates this state through downregulation of its target genes, including genes for amino acid biosynthesis and import. Collectively, we identify a SIRT3-ATF4 axis required to maintain survival of DLBCL cells by enabling them to optimize amino acid uptake and utilization. Targeting ATF4 translation can potentiate the cytotoxic effect of SIRT3 inhibitor to DLBCL cells. SIGNIFICANCE: We discovered the link between SIRT3 and ATF4 in DLBCL cells, which connected lymphoma amino acid metabolism with ATF4 translation via metabolic stress signals. SIRT3-ATF4 axis is required in DLBCL cells regardless of subtype, which indicates a common metabolic vulnerability in DLBCLs and can serve as a therapeutic target.
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.