849P - Long non-coding RNA signatures and their role in the progression of childhood T cell acute lymphoblastic leukemia

Background

Many disease processes are thought to be impacted by altered long non-coding RNAs (lncRNAs) expression. lncRNAs are typically expressed differently throughout healthy and cancerous hematopoiesis. In the domains of haematology and oncology, they represent a class of biomarkers that is receiving increasing attention. According to recent studies, the expression levels of particular lncRNAs are correlated with the prognosis of paediatric patients with acute lymphoblastic leukaemia. To determine the potential roles of lncRNAs involved in pathogenesis of T-ALL, we analyzed the expression profile of lncRNAs in pediatric T-ALL.

Methods

Twenty five pediatric T-All patients were enrolled and subjected to whole transcriptome analysis in comparison with healthy controls. The results from NGS were validated ex vivo, using real time PCR in the same cases and in a different cohort of 25 T-ALL cases and healthy controls. The results were also comapred with public databases in silico. Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes.

Results

A total of 672 differentially expressed lncRNAs were identified. Moreover, the top 10 upregulated lncRNAs were selected and further assessed by RT-qPCR in vitro in the same samples and a different cohort. We found that lncRNAs LINC01221, LINC00977, RP11-472G21.2 and CTD-2291D10.4 were highly over expressed (>10 fold) in the patients while PCAT18, CRNDE, and RP11-620J15.3 showed mild overexpression (2 to 5 fold increase). The expression of these lncRNAs were also increased in Peer and CCRF-CEM cell lines. Finally, expression correlation analyses using weighted gene co-relation analysis of T-ALL selected lncRNAs and mRNAs suggested that lncRNAs LINC01221, LINC00977, CTD-2291D10.4 may play a possible role in lymphocyte activation and cell.

Conclusions

These results showed that several lncRNAs are aberrantly expressed in T-ALL patients and play potential roles in T-ALL development, and can be useful for diagnostic and/or prognostic purposes in pediatric T-ALL. This study provides the keystone to future clinical studies determining the theragnostic value of the characterized long non-coding transcriptome panorama in a clinical setting for childhood patient management.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Post Graduate Institute of Medical Education and Research.

Disclosure

All authors have declared no conflicts of interest.