[August 28] 53rd IRCMS Seminar

August 21 2019

We would like to inform you that the 53rd IRCMS Seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.

Date       : August 28, 2019 (Wednesday)
Time　    : 16:00-17:00
Venue    : IRCMS 1F Meeting Lounge　
Speaker : Shi-Hao TAN, Ph.D.
                Cancer Science Institute of Singapore,
                National University of Singapore

Tilte       : TAL1 Induced Core Regulatory Circuit Regulates Expression of Downstream Oncogenic Factors through Enhancer Associated ncRNA in T-ALL

Abstract:
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 analysed RNA-seq datasets to identify lncRNAs regulated by TAL1 in T-ALL. Our analysis predicted 57 putative lncRNAs that are activated by TAL1, many of which were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We were able to identify novel transcripts that were activated in multiple T-ALL cell samples but absent in normal thymocytes. One of the novel lncRNA transcript near the ARID5B gene locus was named ARIEL (ARID5B Inducing Enhancer-associated Long Non-Coding RNA). ARID5B was recently identified as important for T-ALL leukemogenesis and we further explored the role of the neighbourhood lncRNA ARIEL and other novel enhancer associated ncRNAs in TAL1 positive T-ALL. Overall, our results are one of the first to show that TAL1 regulated enhancer associated ncRNAs play a crucial role in regulating expression of oncogenic factors required for leukemogenesis in T-ALL.

1. Tan SH, Leong WZ, Ngoc PCT, Tan TK, Bertulfo FC, Lim MC, An O, Li Z, Yeoh AEJ, Fullwood MJ, Tenen DG, Sanda T. The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia. Blood. 2019 Jul 18;134(3):239-251
2. Ngoc PCT*, Tan SH*, Tan TK, Chan MM, Li Z, Yeoh AEJ, Tenen DG, Sanda T. Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia. Leukemia. 2018 Oct;32(10):2138-2151. *Co-First Authors
3. Leong WZ, Tan SH, Ngoc PCT, Amanda S, Yam AWY, Liau WS, Gong Z, Lawton LN, Tenen DG, Sanda T. ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis. Genes Dev. 2017 Dec 1;31(23-24):2343-2360.