title: To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients.
abstract: In chronic lymphocytic leukaemia (CLL), the 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 the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples 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 potentially highly specific and sensitive diagnostic approach (AUC = 0.766).
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Piszcz
authors.affiliation: CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Madrid, Spain.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Armitage
authors.affiliation: CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Madrid, Spain.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrarini
authors.affiliation: CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rupérez
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kulczynska
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Bolkun
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Kretowski
authors.affiliation: Clinical Oncology and Hematology Department, Provincial Hospital, Suwalki, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Urbanowicz
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Ciborowski
authors.affiliation: CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Madrid, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D008041:Linoleic Acids / Q000097:blood; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D008041:Linoleic Acids; C116917:acylcarnitine; C420162:linoleamide; D002331:Carnitine
keywords: acylcarnitines; biomarker; chronic lymphocytic leukaemia; disease staging; metabolomics