Thi Ngoc PC1, Tan SH1, Tan TK1, Chan MM1, Li Z2, Yeoh AEJ2,3, Tenen DG1,4,5, Sanda T6,7.
1 Cancer Science Institute of Singapore, National University of Singapore, Singapore
2 Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore
3 VIVA-University Children’s Cancer Centre, Khoo Teck Puat – National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore
4 Harvard Medical School, Boston, Massachusetts, USA
5 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
6 Cancer Science Institute of Singapore, National University of Singapore, Singapore
7 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57 putative lncRNAs that are activated by TAL1. Many of these transcripts were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One transcript near the ARID5B gene locus was specifically expressed in TAL1-positive T-ALL cases. The other transcript located between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic stem cells and T-cell progenitor cells. In addition, we identified a subset of lncRNAs that were negatively regulated by TAL1 and positively regulated by E-proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3-2:7) located near the RORC gene, which was expressed in normal thymocytes but repressed in TAL1-positive T-ALL cells.