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 (1)H-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; 
R(2)=0.74, Q(2)=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 (1)H-NMR-based 
metabolomics as a potential non-invasive prognostic tool for identifying CLL 
disease-state biomarkers.