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Effects of L-leucine in 5q- syndrome and other RPS14-deficient erythroblasts

Leukemia volume 26, pages 2154–2158 (2012)Cite this article

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The 5q- syndrome is the most distinct of all the myelodysplastic syndromes (MDS) with a clear genotype/phenotype relationship. The RPS14 gene, encoding a ribosomal protein and mapping to the commonly deleted region (CDR) of the 5q- syndrome,1 shows haploinsufficiency in the CD34+ cells of patients with this disorder.2, 3 The genes in the 5q- syndrome CDR were studied by an RNA-mediated interference-based approach and it was shown that haploinsufficiency of RPS14 in normal CD34+ cells resulted in a block in erythroid differentiation with relative preservation of megakaryocyte differentiation, suggesting that RPS14 haploinsufficiency is the probable cause of the erythroid defect in this disorder.3 Several lines of converging evidence suggest that p53 activation secondary to ribosomal haploinsufficiency is the mechanism that underlies the anemia in the 5q- syndrome.4, 5

The bone marrow cells of patients with the 5q- syndrome show a block in the processing of pre-ribosomal RNA3 and the CD34+ cells of these patients show deregulation of multiple ribosomal protein genes and genes involved in the control of translation.6 These data suggest that the 5q- syndrome represents a disorder of aberrant ribosome biogenesis.3, 6 Erythroid progenitor cells have a very high rate of proliferation and a requirement for massive globin synthesis, thus necessitating a very high level of ribosome biogenesis and ribosomal activity. This may explain the particular sensitivity of the erythroid lineage to reduced expression levels of ribosomal proteins.5

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Acknowledgements

This work was supported by Leukaemia and Lymphoma Research of the United Kingdom and in part by the National Institute for Health Research of the United Kingdom (Grant NIHR-RP-PG-0310-1004-AN).

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Author notes

  1. B H Yip and A Pellagatti: These authors contributed equally to this work.

Authors and Affiliations

  1. LLR Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK

    B H Yip, A Pellagatti, C Vuppusetty, M Fernandez-Mercado, J S Wainscoat & J Boultwood

  2. Medizinische Klinik II, St Johannes Hospital, Duisburg, Germany

    A Giagounidis

  3. Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany

    U Germing

  4. NDCLS and National Blood Service Oxford Centre, John Radcliffe Hospital, Oxford, UK

    A A Lamikanra & D J Roberts

  5. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK

    E-J McDonald & S Killick

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  1. B H Yip
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Yip, B., Pellagatti, A., Vuppusetty, C. et al. Effects of L-leucine in 5q- syndrome and other RPS14-deficient erythroblasts. Leukemia 26, 2154–2158 (2012). https://doi.org/10.1038/leu.2012.82

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