ZFIN ID: ZDB-PUB-140808-9
L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way
Narla, A., Payne, E.M., Abayasekara, N., Hurst, S.N., Raiser, D.M., Look, A.T., Berliner, N., Ebert, B.L., Khanna-Gupta, A.
Date: 2014
Source: British journal of haematology   167(4): 524-8 (Journal)
Registered Authors: Look, A. Thomas
Keywords: TP53, diamond-blackfan anaemia, haematopoiesis, leucine
MeSH Terms:
  • Anemia, Diamond-Blackfan/drug therapy*
  • Anemia, Diamond-Blackfan/genetics
  • Anemia, Diamond-Blackfan/metabolism
  • Anemia, Diamond-Blackfan/pathology
  • Anemia, Macrocytic/drug therapy*
  • Anemia, Macrocytic/genetics
  • Anemia, Macrocytic/metabolism
  • Anemia, Macrocytic/pathology
  • Animals
  • Chromosome Deletion
  • Chromosomes, Human, Pair 5/genetics
  • Chromosomes, Human, Pair 5/metabolism
  • Cyclin-Dependent Kinase Inhibitor p21/genetics
  • Cyclin-Dependent Kinase Inhibitor p21/metabolism
  • Disease Models, Animal
  • Humans
  • Leucine
  • Ribosomal Proteins/genetics
  • Ribosomal Proteins/metabolism
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 25098371 Full text @ Br. J. Haematol.
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.