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.
Keywords:
TP53; diamond-blackfan anaemia; haematopoiesis; leucine.
© 2014 John Wiley & Sons Ltd.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Diamond-Blackfan / drug therapy*
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Anemia, Diamond-Blackfan / genetics
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Anemia, Diamond-Blackfan / metabolism
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Anemia, Diamond-Blackfan / pathology
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Anemia, Macrocytic / drug therapy*
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Anemia, Macrocytic / genetics
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Anemia, Macrocytic / metabolism
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Anemia, Macrocytic / pathology
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Animals
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Chromosome Deletion
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Chromosomes, Human, Pair 5 / genetics
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Chromosomes, Human, Pair 5 / metabolism
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Disease Models, Animal
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Humans
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Leucine
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Ribosomal Proteins / genetics
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Ribosomal Proteins / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Cyclin-Dependent Kinase Inhibitor p21
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Ribosomal Proteins
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Tumor Suppressor Protein p53
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Zebrafish Proteins
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Leucine
Supplementary concepts
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Chromosome 5q Deletion Syndrome