Serum neuron-specific enolase levels are upregulated in patients with acute lymphoblastic leukemia and are predictive of prognosis

Abstract

We explored the relationship between neuron-specific enolase (NSE) levels and the clinical features of acute lymphoblastic leukemia (ALL). Seventy ALL patients and forty-two healthy controls were enrolled in this study, and their serum NSE levels were measured using an electrochemiluminescence assay. The serum NSE concentration was higher in ALL patients than in healthy controls. In ALL patients, the mean serum NSE level declined after complete remission (CR) but increased with relapse. In addition, the mean serum NSE level was lower in the CR group than in the non-CR group. High NSE levels were associated with poorer progression-free and overall survival than low NSE levels. Serum NSE levels closely correlated with several clinical features, including the immunophenotype, risk stratification and serum lactate dehydrogenase levels. Multivariate analysis revealed that high NSE expression was an independent prognostic factor in adult ALL patients. NSE mRNA levels were also higher in ALL cell lines and bone marrow mononuclear cells from ALL patients than in control cells. These results suggested that NSE could be a clinical prognostic factor and a potential therapeutic target in ALL.

Keywords: acute lymphoblastic leukemia; biomarker; neuron-specific enolase; prognostic factor; targeted therapy.

Figure 1. Serum NSE levels in acute lymphoblastic leukemia patients and healthy controls

The mean concentration of NSE for 70 acute lymphoblastic leukemia patients was 25.01 ng/mL, significantly higher than that of the 42 healthy controls (7.187 ng/mL, P< 0.0001).

Figure 2. ROC curve analysis of the optimal cutoff point for the serum NSE concentration

The most discriminative cutoff value for NSE was 15.2 ng/mL, with an AUC value of 0.886 (P < 0.001). The sensitivity and specificity were 68.6% and 97.6%, respectively.

Figure 3. Serum NSE levels of patients at the time of diagnosis, CR, and relapse

*P<0.05, compared with CR.

Figure 4. Kaplan-Meier survival analysis for all patients with acute lymphoblastic leukemia

Progression-free survival (PFS) and overall survival (OS) were significantly longer in low-NSE patients (≤15.2ng/mL, A, B.) and standard-risk patients C, D. than in high-NSE and high-risk patients, respectively.

Figure 5. NSE mRNA expression in cell lines and bone marrow cells by real-time PCR analysis

A. The NSE levels were significantly higher in all the ALL cell lines than in normal peripheral blood lymphocytes. *P<0.05, compared with normal peripheral blood lymphocytes. B. The NSE levels were significantly higher in the bone marrow mononuclear cells (BM-MCs) of ALL patients than in healthy controls. *P<0.05, compared with BM-MCs of healthy controls.