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Acute lymphoblastic leukemia

Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia

Leukemia volume 32, pages 2138–2151 (2018)Cite this article

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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 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.

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Acknowledgements

We thank Toshio Suda’s laboratory for providing the EML cell line. The research is supported by the National Research Foundation (NRF) Singapore and the Singapore Ministry of Education (MOE) under its Research Centres of Excellence initiative. The research is also supported by the NRF under its Competitive Research Programme (NRF-NRFF2013-02) and the RNA Biology Center at CSI Singapore, NUS, from funding by the Singapore MOE’s Tier 3 grants (MOE2014-T3-1-006). A.E.J.Y. is supported by the National Medical Research Council, Singapore (NMRC/CSA/0053/2013).

Authorship contributions:

P.C.T.N., S.H.T., T.K.T., and T.S. analyzed the results. S.H.T. and M.M.C. performed the experiments. Z.L. and A.E.J.Y. analyzed the data for primary samples. P.C.T.N., S.H.T., D.G.T., and T.S. designed the research. P.C.T.N. and T.S. wrote the paper.

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  1. These authors contributed equally: Phuong Cao Thi Ngoc, Shi Hao Tan.

Authors and Affiliations

  1. Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore

    Phuong Cao Thi Ngoc, Shi Hao Tan, Tze King Tan, Min Min Chan, Daniel G Tenen & Takaomi Sanda

  2. Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore

    Zhenhua Li & Allen. E. J. Yeoh

  3. VIVA–University Children’s Cancer Centre, Khoo Teck Puat–National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore, 119228, Singapore

    Allen. E. J. Yeoh

  4. Harvard Medical School, Boston, Massachusetts, 02215, USA

    Daniel G Tenen

  5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore

    Daniel G Tenen & Takaomi Sanda

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Ngoc, P.C., Tan, S.H., Tan, T.K. et al. Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia. Leukemia 32, 2138–2151 (2018). https://doi.org/10.1038/s41375-018-0110-4

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