ArticleBlood advances2023
Human acute leukemia uses branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 24 citations in OpenAlex.
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Metabolic reprogramming drives pancreatic β cell neogenesis from α cells.Nature chemical biology · 2026Article
- Article
- Suppression of UCP2 alleviates leukemogenesis by enhancing branched-chain amino acids-induced oxidative stress via activating the PI3K/AKT/mTOR signaling pathway.Genes & diseases · 2026Article
- A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- OGFOD1 enables AML chemo- and nutrient stress resistance by regulating protein synthesis.Cell metabolism · 2025Article
- Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential.Cell death discovery · 2025Review
- Role of metabolomic changes in diagnosis and assessment of treatment response in acute myeloid leukemia.Scientific reports · 2025Article
- Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation.Cancer & metabolism · 2025Article
- Unveiling the Maze: Branched-Chain Amino Acids Fueling the Dynamics of Cancer Metabolism and Progression.Cancers · 2025Review
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- Branched-Chain Amino Acid Metabolic Reprogramming and Cancer: Molecular Mechanisms, Immune Regulation, and Precision Targeting.Oncology research · 2025Review
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- High-content stimulated Raman pathology imaging and transcriptomics reveal leukemia subtype-specific lipid metabolic heterogeneity.Frontiers in immunology · 2025Article
- Review
- Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024Review
- BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Crosstalk between autophagy and metabolism: implications for cell survival in acute myeloid leukemia.Cell death discovery · 2024Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-specific metabolic activities play a crucial role in the pathogenesis of human malignancies. To investigate human acute leukemia-specific metabolic properties, we comprehensively measured the cellular metabolites within the CD34+ fraction of normal hematopoietic stem progenitor cells (HSPCs), primary human acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) cells. Here, we show that human leukemia cells are addicted to the branched-chain amino acid (BCAA) metabolism to maintain their stemness, irrespective of myeloid or lymphoid types. Human primary acute leukemias had BCAA transporters for BCAA uptake, cellular BCAA, α-ketoglutarate (α-KG), and cytoplasmic BCAA transaminase-1 (BCAT1) at significantly higher levels than control HSPCs. Isotope-tracing experiments showed that in primary leukemia cells, BCAT1 actively catabolizes BCAA using α-KG into branched-chain α-ketoacids, whose metabolic processes provide leukemia cells with critical substrates for the trichloroacetic acid cycle and the synthesis of nonessential amino acids, both of which reproduce α-KG to maintain its cellular level. In xenogeneic transplantation experiments, deprivation of BCAA from daily diet strongly inhibited expansion, engraftment and self-renewal of human acute leukemia cells. Inhibition of BCAA catabolism in primary AML or ALL cells specifically inactivates the function of the polycomb repressive complex 2, an epigenetic regulator for stem cell signatures, by inhibiting the transcription of PRC components, such as zeste homolog 2 and embryonic ectoderm development. Accordingly, BCAA catabolism plays an important role in the maintenance of stemness in primary human AML and ALL, and molecules related to the BCAA metabolism pathway should be critical targets for acute leukemia treatment.
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.