title: CD5 molecule-like and transthyretin as putative biomarkers of chronic myeloid leukemia - an insight from the proteomic analysis of human plasma.
abstract: 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.
authors.affiliation: School of Biological Sciences, University of the Punjab, Lahore-54590, Pakistan.
authors.forename: Iram
authors.initials: I
authors.lastname: Fatima
authors.affiliation: Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore-54590, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Sadaf
authors.affiliation: Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Syed Ghulam
authors.initials: SG
authors.lastname: Musharraf
authors.affiliation: Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Naghma
authors.initials: N
authors.lastname: Hashmi
authors.affiliation: School of Biological Sciences, University of the Punjab, Lahore-54590, Pakistan.|Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore-54590, Pakistan.
authors.forename: Muhammad Waheed
authors.initials: MW
authors.lastname: Akhtar
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D018956:CD5 Antigens / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011228:Prealbumin / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018956:CD5 Antigens; D011228:Prealbumin