Serum peptidome based biomarkers searching for monitoring minimal residual disease in adult acute lymphocytic leukemia

Ju Bai; Aili He; Chen Huang; Juan Yang; Wanggang Zhang; Jianli Wang; Yun Yang; Pengyu Zhang; Yang Zhang; Fuling Zhou

doi:10.1186/s12953-014-0049-y

Serum peptidome based biomarkers searching for monitoring minimal residual disease in adult acute lymphocytic leukemia

Proteome Sci. 2014 Sep 16;12(1):49. doi: 10.1186/s12953-014-0049-y. eCollection 2014.

Authors

Ju Bai¹, Aili He¹, Chen Huang², Juan Yang², Wanggang Zhang¹, Jianli Wang¹, Yun Yang¹, Pengyu Zhang¹, Yang Zhang¹, Fuling Zhou¹

Affiliations

¹ Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi Province China.
² Department of Genetics and Molecular Biology, Medical school of Xi'an Jiaotong University/Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, Xi'an, 710061 Shaanxi China.

Abstract

Background: The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphocytic leukemia (ALL). This study was to identify serum candidate peptides for monitoring MRD in adult ALL.

Results: A total of 33 peptides in the molecular weight range of 1000-10000 Da were detected using ClinProt system and statistically different between adult patients with ALL and healthy controls. Quick classifier (QC) algorithm was used to obtain a diagnostic model consisting of five peptides that could discriminate patients with ALL from controls with a high sensitivity (100%) and specificity (96.67%). The peptides in the QC model were identified as fibrinogen alpha chain (FGA), glutathione S-transferase P1 (GSTP1), isoform 1 of fibrinogen alpha chain precursor, platelet factor 4 (PF4) by high pressure/performance liquid chromatography mass spectrometry/mass spectrometry. Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL. The peptides with increased relative intensities in newly diagnosed (ND) ALL patients were found to be decreased in their relative intensities after complete remission (CR) of adult ALL. When ALL patients were refractory & relapsed (RR), relative intensities of the peptides were elevated again. Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR. The findings were validated by ELISA and western blot. Further linear regression analyses were performed to eliminate the influence of platelet and white blood cell counts on serum protein contents and indicated that there were no correlations between the contents of all four proteins (PF4, connective tissue active peptide III, FGA and GSTP1) and white blood cell or platelet counts in ALL different groups and healthy control.

Conclusions: We speculate the five peptides, FGA, isoform 1 of fibrinogen alpha chain precursor, GSTP1, PF4 and connective tissue active peptide III would be potential biomarkers for forecasting relapse, monitoring MRD and evaluating therapeutic response in adult ALL.

Keywords: Adult acute lymphocytic leukemia; Biomarker; Minimal residual disease; Serum peptidome.