Overexpression of ZEB2-AS1 lncRNA is associated with poor clinical outcomes in acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy with poor clinical outcomes. To determine whether the expression of the long non-coding (lnc)RNA zinc finger E-box binding homeobox 2 (ZEB2) antisense RNA 1 (ZEB2-AS1) is associated with clinical outcomes, its expression was analyzed in a retrospective cohort of 62 AML and 10 non-malignant cases. The results revealed that the expression of ZEB2-AS1 lncRNA was notably high and closely associated with adverse clinical outcomes in AML cases compared with the non-malignant cases, based on either modified Medical Research Council or European Leukemia Net risk stratification systems. Univariate analyses indicated that patients with a higher expression of ZEB2-AS1 lncRNA had significantly shorter overall survival (OS) (P=0.036) and disease-free survival (DFS) rates (P=0.039) compared with patients with a lower expression of ZEB2-AS1 lncRNA. In addition, patients with a higher expression of ZEB2-AS1 lncRNA had a significant lower complete remission rate in response to induction by chemotherapy compared with patients with a lower expression of ZEB2-AS1 lncRNA (P=0.031). In cases with low levels of ZEB2-AS1 lncRNA, patients treated with allogenic hematopoietic stem cell transplantation had significantly longer OS and DFS rates compared with that of chemotherapy-treated patients (P=0.037 and P=0.049 respectively). Furthermore, the knockdown of ZEB2-AS1 lncRNA effectively inhibited AML cell invasion and migration, which was closely associated with the downregulation of ZEB2 and upregulation of E-cadherin expression. Collectively, although its independent prognostic value for survival was not rigorously determined, ZEB2-AS1 lncRNA may function as a candidate marker to improve conventional risk stratification systems and the evaluation of therapeutic responses for AML.