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Long Non-coding RNAs in the Development and Maintenance of Lymphoid Malignancies

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Molecular Biology of Long Non-coding RNAs

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Abstract

The development of lymphoid cells (i.e. B and T cells) is a complicated process involving various differentiation substages in bone marrow, thymus, lymph nodes and the circulation. Long noncoding (lnc)RNAs are in many ways involved in both normal lymphoid development and malignant transformation of lymphoid cells. In this chapter, we give an overview of the current state of knowledge on the diverse roles of lncRNAs in lymphoid malignancies. One remarkable finding is the direct involvement of lncRNA transcription in genome integrity and malignant transformation. B and T cell receptor rearrangements involve the introduction of double strand DNA breaks followed by their directed repair. LncRNA transcription was associated with off-targeting of endonucleases introducing these double strand breaks, which can lead to chromosomal translocation of oncogene loci, and as a consequence aberrant expression and development of a malignancy. Oncogenic fusion genes present in a subset of T-cell malignancies were furthermore shown to influence expression of a subset of lncRNAs. These expression changes in turn, were directly linked to oncogenic pathways, treatment response and patient outcome. Overexpression of oncogenes also induced changes in lncRNA expression patterns. These oncogene-regulated lncRNAs in turn play essential roles in the mediation of the downstream effects of the respective oncogene. In addition, some lncRNAs are involved in the upstream regulation of common oncogenes. We furthermore discuss a few specific lncRNAs that have been functionally characterized in detail in one or multiple lymphoid cancers. Lastly, we address noncoding genome variants and their association with the susceptibility to lymphoid malignancies. We conclude that lncRNAs are major players in all aspects of lymphoid development and malignant transformation. This strongly suggests that lncRNAs can be exploited for prognostic and therapeutic purposes in lymphoid malignancies in the future.

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Authors and Affiliations

  1. Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands

    Melanie Winkle, Joost Kluiver & Anke van den Berg

  2. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

    Agnieszka Dzikiewicz-Krawczyk

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  1. Melanie Winkle
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  2. Agnieszka Dzikiewicz-Krawczyk
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  3. Joost Kluiver
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  4. Anke van den Berg
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Correspondence to Joost Kluiver .

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Editors and Affiliations

  1. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Ahmad M. Khalil

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Winkle, M., Dzikiewicz-Krawczyk, A., Kluiver, J., van den Berg, A. (2019). Long Non-coding RNAs in the Development and Maintenance of Lymphoid Malignancies. In: Khalil, A. (eds) Molecular Biology of Long Non-coding RNAs. Springer, Cham. https://doi.org/10.1007/978-3-030-17086-8_6

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