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Br J Haematol. 2014 Nov;167(4):524-528. doi: 10.1111/bjh.13069. Epub 2014 Aug 7.

L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way.

Author information

1
Division of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University School of Medicine, CCSR-1215b, 269 Campus Drive, Stanford, CA 94305-5162.
2
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Karp 5-2117, 1 Blackfan Circle, Boston, MA, 02115.
3
University College London, 334 Paul O'Gorman Building, 72 Huntley Street, London. WC1E 6BT.
4
National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London W1T 7DN.
5
Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
#
Contributed equally

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

PMID:
25098371
PMCID:
PMC4211992
DOI:
10.1111/bjh.13069
[Indexed for MEDLINE]
Free PMC Article

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