Oncotarget

Research Papers:

To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients

Jaroslaw Piszcz, Emily G. Armitage, Alessia Ferrarini, Francisco J. Rupérez, Agnieszka Kulczynska, Lukasz Bolkun, Janusz Kloczko, Adam Kretowski, Alina Urbanowicz, Michal Ciborowski and Coral Barbas _

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Oncotarget. 2016; 7:22324-22338. https://doi.org/10.18632/oncotarget.8078

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Abstract

Jaroslaw Piszcz1,*, Emily G. Armitage2,*, Alessia Ferrarini2, Francisco J. Rupérez2, Agnieszka Kulczynska1, Lukasz Bolkun1, Janusz Kloczko1, Adam Kretowski3, Alina Urbanowicz4, Michal Ciborowski3, Coral Barbas2

1Department of Haematology, Medical University of Bialystok, Bialystok, Poland

2CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Madrid, Spain

3Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland

4Clinical Oncology and Hematology Department, Provincial Hospital, Suwalki, Poland

*These authors contributed equally to this work

Correspondence to:

Coral Barbas, e-mail: [email protected]

Michal Ciborowski, e-mail: [email protected]

Keywords: chronic lymphocytic leukaemia, metabolomics, disease staging, biomarker, acylcarnitines

Received: September 15, 2015     Accepted: February 23, 2016     Published: March 14, 2016

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).


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