Evaluation of Methylation at Promoter Regions of Long Non-coding RNAs in Patients with Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups. Methods: In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium bisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, andRP11-68118.10 were evaluated using methylation specific‑high resolution melting (MS‑HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests. Results: The methylation levels of all studied lncRNAs including RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were significantly increased (p<0.05). ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers. Conclusion: This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.

Keywords

• long non-coding rna
• acute lymphoblastic leukemia
• oncogenesis
• methylation