title: L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way.
abstract: Haploinsufficiency of ribosomal proteins (RPs) and upregulation of the tumour suppressor TP53 have been shown to be the common basis for the anaemia observed in Diamond Blackfan anaemia and 5q- myelodysplastic syndrome. We previously demonstrated that treatment with L-Leucine resulted in a marked improvement in anaemia in disease models. To determine if the L-Leucine effect was Tp53-dependent, we used antisense MOs to rps19 and rps14 in zebrafish; expression of tp53 and its downstream target cdkn1a remained elevated following L-leucine treatment. We confirmed this observation in human CD34+ cells. L-Leucine thus alleviates anaemia in RP-deficient cells in a TP53-independent manner.
authors.affiliation: Division of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University School of Medicine, CCSR-1215b, 269 Campus Drive, Stanford, CA 94305-5162.|Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Anupama
authors.initials: A
authors.lastname: Narla
authors.affiliation: University College London, 334 Paul O'Gorman Building, 72 Huntley Street, London. WC1E 6BT.|National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London W1T 7DN.
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: Payne
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Nirmalee
authors.initials: N
authors.lastname: Abayasekara
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Slater N
authors.initials: SN
authors.lastname: Hurst
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: David M
authors.initials: DM
authors.lastname: Raiser
authors.affiliation: Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
authors.forename: Arati
authors.initials: A
authors.lastname: Khanna-Gupta
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000748:Anemia, Macrocytic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007930:Leucine; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D007930:Leucine
keywords: TP53; diamond-blackfan anaemia; haematopoiesis; leucine
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