Long non‑coding RNA ANRIL is a potential indicator of disease progression and poor prognosis in acute myeloid leukemia

Abstract

The present study explored the association of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) with the development of acute myeloid leukemia (AML) clinical features and prognosis of patients with AML. Bone marrow mononuclear cells (BMMCs) were obtained from 178 patients with de novo AML prior to initial therapy and from 30 healthy donors. The expression of lncRNA ANRIL in BMMCs was detected by reverse transcription-quantitative PCR. Complete remission (CR) was assessed after induction therapy. Event-free survival (EFS) and overall survival (OS) were evaluated during the follow-up. The levels of lncRNA ANRIL were increased in patients with AML compared with those in healthy donors and were capable of distinguishing patients with AML from healthy donors (area under the curve, 0.886; 95% CI, 0.820-0.952). Furthermore, lncRNA ANRIL was associated with an increased occurrence internal tandem duplications in the FMS-like tyrosine kinase 3, decreased occurrence inv(16) or t(16;6), intermediate-risk and poor-risk stratification while no association of lncRNA ANRIL was identified with French-American-British classification, cytogenetics, isolated biallelic CCAAT/enhancer-binding protein α mutation and nucleophosmin 1 mutation in patients with AML. Furthermore, lncRNA ANRIL was significantly associated with a lower CR rate. In addition, EFS and OS were shorter in patients with high expression of lncRNA ANRIL compared with those in patients with low expression of lncRNA ANRIL. Multivariate Cox regression analyses revealed that high expression of lncRNA ANRIL, poor-risk stratification and white blood cells (>10.0x10 9 cells/l) were independent prognostic factors for shorter EFS, while high expression of lncRNA ANRIL and poorer risk stratification were independent prognostic factors for shorter OS. The present results suggested that lncRNA ANRIL has clinical relevance as a biomarker for assisting diagnosis treatment decisions and prognosis prediction and the identification of potential drug target for AML.

Prognostic Significance of Long Non Coding RNA ANRIL and SNHG14 in Acute Myeloid Leukemia

“…In the present study, we revealed that lnRNA ANRIL and SNHG14 were overexpressed in AML patients, suggesting they play a role in AML development and prognosis. Similarly, previous research reported that lnRNA ANRIL and lnRNA SNHG14 were overexpressed in AML patients' samples compared to healthy controls (Tan et al, 2021;Wang et al, 2021).…”

“…Moreover, we demonstrated that it was associated with high FLT3-ITD and low NPM-1 mutations in AML . Similarly, a study carried out by Tan et al, (2021) proved that lnRNA ANRIL was significantly associated with AML development, FLT3 mutation and low CR, RFS and OS. Therefore, we can say that lnRNA ANRIL is associated with poor prognosis in AML.…”

“…For example, LINC01018 was found to be downregulated in AML and its upregulation inhibited AML cell growth and might provide therapeutic evidence in the future (Zhou et al, 2021) . On the other hand, lncRNA CD27 Antisense RNA 1 (CD27-AS1) was found to be overexpressed in AML and might be a potential prognostic marker for AML in the future (Tao et al, 2021) . In the present study, we revealed that lnRNA ANRIL and SNHG14 were overexpressed in AML patients, suggesting they play a role in AML development and prognosis.…”

Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia

“…High ANRIL expression was able to differentiate AML patients from healthy donors with high specificity. High expression of ANRIL has been correlated with shorter event‐free survival as well as overall survival in AML (Tan et al, 2021). The high expression of ANRIL was observed to downregulate the expression of miRNA‐34a, thereby resulting in HDAC1 overexpression, which prevents the recruitment of E2F1 to ASPP2.…”

LncRNAs has been identified as regulators of Myeloid-derived suppressor cells in lung cancer

“…Therefore, ANRIL was proposed as a biomarker for AML. Moreover, it has clinical relevance in assisting the diagnosis, treatment and prognosis prediction of AML and identifying potential drug targets of AML ( 131 ).…”