Monitoring TKI therapeutic responses with the panel of metabolic biomarkers in the chronic myeloid leukemia patients

Abstract

To investigate the potential biomarkers associated with Chronic Myeloid Leukemia (CML), reveal the metabolite changes related to the continuous phases of tyrosine kinase inhibitors (TKI) and find the potential biomarkers associated with treatment effects. 52 patients with CML and matched 26 healthy people were enrolled as discovery set. Another 194 randomly selected CML patients treated with TKI were chosen as external validation set. Plasma samples from the patients and controls were profiled by using gas chromatography-mass spectrometry (GC-MS) based metabonomic approach. Multivariate and univariate statistical analysis were combined to select the differential metabolic features. GC-MS-based metabolomics showed a clear clustering and separation of metabolic patterns from healthy control, pre- and post-TKI treatment CML patients in the discovery set. We identified nine metabolites that differentiated CML patients from healthy controls, including lactic acid, isoleucine, glycerol, glycine, myristic acid, D-sorbitol, D-galactose, D-glucose and myo-inositol. Among the 9 markers, glycerol and myristic acid had the most significant association with TKI treatment effects in both discovery and external validation set. In the ROC analysis, combination of glycerol and myristic acid showed a better discrimination performance compared to a single biomarker. The results indicated that metabolic profile has the potential for diagnosis of CML and the panel of biomarkers including myristic acid and glycerol may be useful in monitoring TKI therapeutic responses.

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