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Molecular Targets for Therapy

Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia

Leukemia volume 20, pages 1731–1737 (2006)Cite this article

Abstract

The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.

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Acknowledgements

We would like to thank Dr David Baker, Dr Nicholas Gottardo and staff of the Princess Margaret Hospital, Perth for their invaluable support, as well as the patients and parents involved in this study. We are grateful to Dr Lawrence Abraham for his critical evaluation of the manuscript. This work was supported by the National Health and Medical Research Council and the Children's Leukaemia and Cancer Research Foundation, Perth, Australia.

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Authors and Affiliations

  1. Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, Perth, Western Australia, Australia

    J M Boag, A H Beesley, J R Freitas, J Ford, K Hoffmann, A J Cummings & U R Kees

  2. Division of Biostatistics and Genetic Epidemiology, Telethon Institute for Child Health Research, Perth, Western Australia, Australia

    M J Firth & N H de Klerk

  3. Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia

    M J Firth & N H de Klerk

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  1. J M Boag
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Correspondence to U R Kees.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Boag, J., Beesley, A., Firth, M. et al. Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia. Leukemia 20, 1731–1737 (2006). https://doi.org/10.1038/sj.leu.2404365

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