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.
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Authors | Anupama Narla, Elspeth M Payne, Nirmalee Abayasekara, Slater N Hurst, David M Raiser, A Thomas Look, Nancy Berliner, Benjamin L Ebert, Arati Khanna-Gupta |
Journal | British journal of haematology
(Br J Haematol)
Vol. 167
Issue 4
Pg. 524-528
(Nov 2014)
ISSN: 1365-2141 [Electronic] England |
PMID | 25098371
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 John Wiley & Sons Ltd. |
Chemical References |
- Cyclin-Dependent Kinase Inhibitor p21
- Ribosomal Proteins
- Tumor Suppressor Protein p53
- Zebrafish Proteins
- Leucine
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Topics |
- Anemia, Diamond-Blackfan
(drug therapy, genetics, metabolism, pathology)
- Anemia, Macrocytic
(drug therapy, genetics, metabolism, pathology)
- Animals
- Chromosome Deletion
- Chromosomes, Human, Pair 5
(genetics, metabolism)
- Cyclin-Dependent Kinase Inhibitor p21
(genetics, metabolism)
- Disease Models, Animal
- Humans
- Leucine
- Ribosomal Proteins
(genetics, metabolism)
- Tumor Suppressor Protein p53
(genetics, metabolism)
- Zebrafish Proteins
(genetics, metabolism)
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