Abstract
BackgroundAcute lymphoblastic leukemia is the most common malignant cancer in childhood. The signs and symptoms of childhood cancer are difficult to recognize, as it is not the first diagnosis to be considered for nonspecific complaints, leading to potential uncertainty in diagnosis. The aim of this study was to perform proteomic analysis of serum from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to identify candidate biomarker proteins, for use in early diagnosis and evaluation of treatment.MethodsSerum samples were obtained from ten patients at the time of diagnosis (B-ALL group) and after induction therapy (AIT group). Sera from healthy children were used as controls (Control group). The samples were subjected to immunodepletion, affinity chromatography with α-d-galactose-binding lectin (from Artocarpus incisa seeds) immobilized on a SepharoseTM 4B gel, concentration, and digestion for subsequent analysis with nano-UPLC tandem nano-ESI-MSE. The program ExpressionE was used to quantify differences in protein expression between groups.ResultsA total of 96 proteins were identified. Leucine-rich alpha-2-glycoprotein 1 (LRG1), Clusterin (CLU), thrombin (F2), heparin cofactor II (SERPIND1), alpha-2-macroglobulin (A2M), alpha-2-antiplasmin (SERPINF2), Alpha-1 antitrypsin (SERPINA1), Complement factor B (CFB) and Complement C3 (C3) were identified as candidate biomarkers for early diagnosis of B-ALL, as they were upregulated in the B-ALL group relative to the control and AIT groups. Expression levels of the candidate biomarkers did not differ significantly between the AIT and control groups, providing further evidence that the candidate biomarkers are present only in the disease state, as all patients achieved complete remission after treatment.ConclusionA panel of protein biomarker candidates has been developed for pre-diagnosis of B-ALL and also provided information that would indicate a favorable response to treatment after induction therapy.
Highlights
Acute lymphoblastic leukemia is the most common malignant cancer in childhood
Leucine-rich alpha-2-glycoprotein 1 (LRG1), Clusterin (CLU), thrombin (F2), heparin cofactor II (SERPIND1), alpha-2-macroglobulin (A2M), alpha-2antiplasmin (SERPINF2), Alpha-1 antitrypsin (SERPINA1), Complement factor B (CFB) and Complement C3 (C3) were over-expressed in the B-Acute lymphoblastic leukemia (ALL) compared to the control and AIT groups, and were identified as candidate biomarkers for early diagnosis of BALL
The AIT group showed no significant differences in the expression levels of these proteins, compared to the control group, did not show any significant change in the level of expression of these proteins, a fact that further reaffirms the presence of these potential biomarkers in a disease state, as all patients achieved complete remission after treatment (Fig. 2)
Summary
Acute lymphoblastic leukemia is the most common malignant cancer in childhood. The signs and symptoms of childhood cancer are difficult to recognize, as it is not the first diagnosis to be considered for nonspecific complaints, leading to potential uncertainty in diagnosis. The aim of this study was to perform proteomic analysis of serum from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to identify candidate biomarker proteins, for use in early diagnosis and evaluation of treatment. Acute lymphoblastic leukemia (ALL) is the most common malignant cancer in childhood, and is responsible for approximately 25 % of all childhood cancers and 72 % of all cases of pediatric leukemia [1]. The preclinical phase of biomarker discovery was applied and a proteomic analysis of serum samples from pediatric patients with B-ALL was performed, to analyze levels of glycoprotein expression, with the aim of identifying biomarkers to aid in the early diagnosis of BALL and to assess the response to induction therapy
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