To Treat or Not to Treat: Metabolomics Reveals Biomarkers for Treatment Indication in Chronic Lymphocytic Leukaemia Patients

In chronic lymphocytic leukaemia (CLL) clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In this research we reached for LC-MS metabolic fingerprinting method to analyse serum of stable (n=51) and progressive (n=42) CLL patients and controls (n=45) with aim to discover metabolic indicators of disease status. A panel of markers discriminating aggressive from indolent patients was discovered. Ten of them were selected for validation on larger population (45 controls and 92 CLL) with an independent analytical technique. Linoleamide (p=0.002) in addition to various acylcarnitines (p=0.001-0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p=0.05) and hexannoylcarnitine (p=0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a highly specific and sensitive diagnostic approach (AUC=0.766).