Potential biomarkers for adult acute myeloid leukemia minimal residual disease assessment searched by serum peptidome profiling

Background: Post treatment minimal residual disease (MRD) determination contributes to impending relapse prediction, chemotherapy response and clinical outcomes assessment, guiding clinicians to develop reasonable and effective individual chemotherapy options after induction/consolidation. This study was to identify serum candidate peptides for monitoring adult acute myeloid leukemia (AML) MRD. Results: 47 statistically different expressed peptide peaks were obtained in the molecular weight range of 700-10000 Da. Quick classifier (QC) model had optimal distinction efficiency, in the training set with a sensitivity of 90% and a specificity of 93.33%. Peptides were identified as ubiquitin-like modifier activating enzyme 1(UBA1), isoform 1 of fibrinogen alpha chain precursor and platelet factor 4(PF4). The peptide up-regulated in newly diagnosed AML patients were decreased to the normal level after CR. When refractory & relapsed, relative intensity was elevated again. Results were contrary to down-regulated peptide peaks. Western blot demonstrated that levels of the UBA1 protein did not differ between the leukemia and normal cells. Levels of isoform 1 of fibrinogen alpha chain precursor protein and PF4 protein were both decreased in leukemia cells comparing with normal cells. The serum levels of the PF4 in the newly diagnosed AML patients and healthy controls were significantly different. Further correlation analysis did not indicate the correlated relation between platelet counts and PF4 content, the correlation coefficient was 0.097. Kaplan-Meier analyses of overall survival showed that relative intensity of peptides was correlated with patient's clinical outcome. Conclusions: We speculate the peptides can be used as potential markers for monitoring minimal residual disease and clinical outcome assessment.