ArticleBlood2012
L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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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.
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Who cites it
102 citing papers in PubMed, 169 citations in OpenAlex.
- L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.Pediatric blood & cancer · 2020Trial
- Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Established and emerging non-cellular therapies in inherited bone marrow failure syndromes.Frontiers in immunology · 2026Review
- Systematic analysis of noncanonical ribosomal protein paralogs does not provide evidence for specialized functions inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- Review
- A novel mouse model to study the effects of new therapies for Diamond-Blackfan anemia.Blood advances · 2025Article
- Disruption of mitochondrial energy metabolism is a putative pathogenesis of Diamond-Blackfan anemia.iScience · 2024Article
- Nucleic acid-induced inflammation on hematopoietic stem cells.Experimental hematology · 2024Article
- Recapitulating and reversing human brain ribosomopathy defects via the maladaptive integrated stress response.Science advances · 2024Article
- Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management.Journal of clinical medicine · 2023Review
- Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.PLoS genetics · 2023Article
- Gene therapy for congenital marrow failure syndromes - no longer grasping at straws?Haematologica · 2023Article
- Comparative analyses of dynamic transcriptome profiles highlight key response genes and dominant isoforms for muscle development and growth in chicken.Genetics, selection, evolution : GSE · 2023Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Nucleolar Protein 56 Deficiency in Zebrafish Leads to Developmental Abnormalities and Anemia viaBiology · 2023Article
- Article
- Hematopoietic cell transplantation and gene therapy for Diamond-Blackfan anemia: state of the art and science.Frontiers in oncology · 2023Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation. This resulted in a striking improvement of the anemia associated with RP loss. We confirmed our findings in primary human CD34⁺ cells, after shRNA knockdown of RPS19 and RPS14. Furthermore, we showed that loss of Rps19 or Rps14 activates the mTOR pathway, and this is accentuated by L-leucine in both Rps19 and Rps14 morphants. This effect could be abrogated by rapamycin suggesting that mTOR signaling may be responsible for the improvement in anemia associated with L-leucine. Our studies support the rationale for ongoing clinical trials of L-leucine as a therapeutic agent for DBA, and potentially for patients with del(5q) MDS.
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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.