Better and sensitive
biomarkers are needed to help understand the mechanism of disease onset, progression, prognosis and monitoring of the therapeutic response. Aim of this study was to identify the candidate circulating markers of chronic-phase
chronic myeloid leukemia (CP-CML) manifestations, having potential to develop into predictive- or monitoring-
biomarkers. A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose. Based on the spot intensity measurements, six
proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0.05]. These were identified as α-1-antichymotrypsin, α-1-antitrypsin, CD5 molecule-like, stress-induced
phosphoprotein 1,
vitamin D binding protein isoform 1 and
transthyretin by MS analysis [PMF score ≥79; data accessible via ProteomeXchange with identifier PXD002757]. Quantitative ELISA, used for validation of candidate
proteins both in the pre-treated and
nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like,
transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based
therapy (ANOVA p < 0.0001). Two of the circulating marker
proteins, identified in this study, had not previously been associated with chronic- or acute-phase
myeloid leukemia. Exploration of their probable association with CP-CML, in a larger study cohort, may add to our understanding of the disease mechanism besides developing clinically useful
biomarkers in future.