L‐Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q‐ syndrome in a TP 53‐independent way
Year: 2014
Type: article
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.
Source: British Journal of Haematology
DOI: 10.1111/bjh.13069
Institutions: Brigham and Women's Hospital, Lucile Packard Children's Hospital, Harvard University, Stanford Medicine, Stanford University, National Institute for Health and Care Research, UCL Biomedical Research Centre, University College London, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G4070601418, G723735978, G8646381853
OpenAlex ID: W2106322008