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Chronic Lymphocytic Leukemia

Serum metabolome analysis by 1H-NMR reveals differences between chronic lymphocytic leukaemia molecular subgroups

Leukemia volume 24, pages 788–797 (2010)Cite this article

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Abstract

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease exhibiting variable clinical course and survival rates. Mutational status of the immunoglobulin heavy chain variable regions (IGHVs) of CLL cells offers useful prognostic information for high-risk patients, but time and economical costs originally prevented it from being routinely used in a clinical setting. Instead, alternative markers of IGHV status, such as zeta-associated protein (ZAP70) or messenger RNA levels are often used. We report a 1H-NMR-based metabolomics approach to examine serum metabolic profiles of early stage, untreated CLL patients (Binet stage A) classified on the basis of IGHV mutational status or ZAP70. Metabolic profiles of CLL patients (n=29) exhibited higher concentrations of pyruvate and glutamate and decreased concentrations of isoleucine compared with controls (n=9). Differences in metabolic profiles between unmutated (UM-IGHV; n=10) and mutated IGHV (M-IGHV; n=19) patients were determined using partial least square discriminatory analysis (PLS-DA; R2=0.74, Q2=0.36). The UM-IGHV patients had elevated levels of cholesterol, lactate, uridine and fumarate, and decreased levels of pyridoxine, glycerol, 3-hydroxybutyrate and methionine concentrations. The PLS-DA models derived from ZAP70 classifications showed comparatively poor goodness-of-fit values, suggesting that IGHV mutational status correlates better with disease-related metabolic profiles. Our results highlight the usefulness of 1H-NMR-based metabolomics as a potential non-invasive prognostic tool for identifying CLL disease-state biomarkers.

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Acknowledgements

We thank the Spanish Ministerio de Ciencia e Innovación (MCINN, SAF2008-01845), Instituto de Salud Carlos III (PI061001/IF07/3611-1), Generalitat Valenciana (GVPRE/2008/193) for financial support and Bruker Biospin for technical and economic contributions. DAM is a Marie Curie International Incoming Fellow (PIIF-GA-2008-221484). BJ is supported by a Fondo de Investigación Sanitario Post Doctoral grant (CD2006/00133).

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Authors and Affiliations

  1. Structural Biology Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain

    D A MacIntyre, B Jiménez & A Pineda-Lucena

  2. Molecular Haematology Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain

    E Jantus Lewintre, C Reinoso Martín & J García-Conde

  3. Bruker BioSpin GmbH, Rheinstetten, Germany

    H Schäfer & M Spraul

  4. Haematology Service, Hospital Arnau de Vilanova, Valencia, Spain

    C García Ballesteros & J Ramón Mayans

  5. Medicine Department, University of Valencia, Valencia, Spain

    J García-Conde

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  1. D A MacIntyre
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MacIntyre, D., Jiménez, B., Lewintre, E. et al. Serum metabolome analysis by 1H-NMR reveals differences between chronic lymphocytic leukaemia molecular subgroups. Leukemia 24, 788–797 (2010). https://doi.org/10.1038/leu.2009.295

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