Prognostic Implication of MIF Gene Expression in Childhood Acute Lymphoblastic Leukemia.

Abstract

Cytogenetic and molecular genetic markers have been used recently to stratify risk and predict prognosis of different types of cancers. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of many diseases, such as autoimmune diseases and cancers. We studied MIF gene expression behavior to investigate its prognostic impact in childish patients with acute lymphoblastic leukemia (ALL). MIF expression was analyzed using quantitative real-time (QRT) PCR. Patients are classified into two groups, high and low MIF expressers, according to median MIF gene expression. We did not find any significant difference between both groups as regards the clinical and hematological picture. However, high MIF expressers had significantly lower incidence of CR (25.8% vs. 72.4%, p = 0.001), higher incidence of refractory (51.6% vs. 24.1, p = 0.029), relapse rates (19.4% vs. 10.3%, p = 0.32), and higher mortality rate (54.8% vs. 20.7, p = 0.007) than lower MIF expressers. In addition, high MIF expressers show significantly shorter DFS (12.48 vs. 25.11 months, cumulative survival 38.7% vs. 72.2%, p < 0.01) and inferior overall survival (20.61 vs. 29.74 months, cumulative survival 45.2% vs. 79.3%, p < 0.001) than low MIF expressers. Multivariate cox-regression analysis adjustment confirmed that high MIF expression was the only independent prognostic factor in ALL patients for OS and DFS in our study (p = 0.004, p = 0.01 respectively). We found that MIF expression is an important prognostic factor in ALL patients with normal karyotype, and its incorporation into novel risk-adapted therapeutic strategies will improve the current cure rates for this group of patients.