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Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia

Leukemia volume 30, pages 1927–1930 (2016)Cite this article

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of immature developing precursor T-cells and can be classified into different molecular genetic subgroups based on the aberrant activation of particular transcription factor oncogenes. In addition, these distinct molecular entities display specific gene expression signatures and can be linked to certain stages of T-cell development.1, 2, 3, 4 Most genetic subtypes of human T-ALL are named after the transcription factor oncogene that is predominantly altered in these hematological tumors, that is, TAL/LMO, TLX1 (HOX11), TLX3 (HOX11L2) or HOXA. However, immature T-ALLs, which generally lack a unifying molecular genetic alteration, are also considered as a separate T-ALL entity with putative clinical relevance.

Long noncoding RNAs (lncRNAs) are a novel class of untranslated RNAs that are at least 200 nucleotides in size and are implicated in a wide variety of cellular functions and specific developmental processes. Notably, recent studies have shown that lncRNAs can drive tumor development5, 6 and, in the context of T-ALL, it has been described that NOTCH1 regulates the expression of several lncRNAs.7, 8 One interesting example is LUNAR1, which enhances the expression of IGF1R, leading to sustained IGF1 signaling.8 Thus far, lncRNAs remained unexplored as genetic markers for distinct T-ALL subtypes.

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Acknowledgements

We thank the following funding agencies: the Fund for Scientific Research Flanders (‘FWO Vlaanderen’ research projects 3G056413N and 3G055013N to FS; G065614, 3GA00113N and G.0C47.13N to PVV and G037514N and G0B2913 to TT; ‘Kom op tegen Kanker’ project G0E3514N to FS; PhD grant to AW; postdoctoral grants to IvdW, PR and PM), IWT Vlaanderen (PhD grant to DR), the Belgian Foundation against Cancer (FS), Ghent University Research Fund (GOA GENT-Lung (FAC)), the Cancer Plan from the Federal Public Service of Health (FS), The Children Cancer Fund Ghent (FS), the Flemish League against Cancer (PhD grant to KD, postdoctoral grant to FM), the Belgian Program of Interuniversity Poles of Attraction (IUAP P7/03) and the Multidisciplinary Research Partnership ‘Bioinformatics: From Nucleotides to Networks’ Project of Ghent University (01MR0310W to PJV). The computational resources (Stevin Supercomputer Infrastructure) and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by Ghent University, the Hercules Foundation and the Flemish Government department EWI. We thank Aline Eggermont for excellent technical assistance.

Author contributions

AW performed and analyzed experiments and wrote the paper; KD, WVL, IVdW, FM, FAC and DR performed experiments; PJV, PM and JV designed the array and set-up the analysis; TT and JS provided samples; PR, BP, PVV and FS designed experiments, directed research and wrote the paper. All the authors read and edited the manuscript.

Access to data

The cell line expression data and ChIP-Seq data of the LOUCY cell line has been deposited in GEO (GSE74312). In Supplementary Information you can find the results of the performed analyses.

Author information

Author notes

  1. P Van Vlierberghe and F Speleman: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium

    A Wallaert, K Durinck, W Van Loocke, F Matthijssens, P J Volders, F Avila Cobos, D Rombaut, P Rondou, P Mestdagh, J Vandesompele, B Poppe, P Van Vlierberghe & F Speleman

  2. Cancer Research Institute Ghent (CRIG), Ghent, Belgium

    A Wallaert, K Durinck, F Matthijssens, P J Volders, F Avila Cobos, D Rombaut, P Rondou, P Mestdagh, J Vandesompele, B Poppe, T Taghon, P Van Vlierberghe & F Speleman

  3. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium

    I Van de Walle & T Taghon

  4. Genome Rearrangements and Cancer Laboratory, U944 INSERM, University Paris Diderot and Hematology Laboratory, Saint-Louis Hospital, Paris, France

    J Soulier

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  1. A Wallaert
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Corresponding authors

Correspondence to A Wallaert or F Speleman.

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Supplementary Information accompanies this paper on the Leukemia website .

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Wallaert, A., Durinck, K., Van Loocke, W. et al. Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia. Leukemia 30, 1927–1930 (2016). https://doi.org/10.1038/leu.2016.82

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