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The Molecular Basis of B Cell Development and the Role of Deregulated Transcription and Epigenetics in Leukaemia and Lymphoma

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Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development

Part of the book series: Epigenetics and Human Health ((EHH))

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Abstract

The development of B cells from their haematopoietic stem cell origins relies on a network of transcription factors that centre on PU.1, Ikaros and Pax5. These transcription factors cooperate to direct progenitor cells towards the early B cell lineage. Further maturation is then dependent on the process of V(D)J recombination, which creates a population of B cells expressing a hugely diverse repertoire of antigen receptors on their cell surface. When an antigen is bound by its cognate receptor, the antigen–antibody interaction is fine-tuned by somatic hypermutation (SHM) and the immune response is expanded by class switch recombination (CSR), which creates antibodies with different effector functions. The processes of V(D)J recombination, SHM and CSR all involve either the breaking or mutating of genomic DNA. Mistakes in any of these reactions can lead to chromosome translocations, which are thought to be the key event that triggers almost all lymphoid cancers. The first part of this review will discuss the transcriptional and epigenetic changes that lead to B cell lineage commitment, whilst the second part will cover the deregulation of these processes and their role in triggering B cell leukaemias and lymphomas. Lastly, we discuss recent advances in our understanding of the role of deregulated epigenetic and transcription factors in the development of B cell cancers.

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Acknowledgments

This work was funded by an EPSRC studentship (to CMK) a Lady Tata Memorial Trust studentship (to JNS), a MRC grant G0801101 (to JB) and the BBSRC (SB).

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Authors and Affiliations

  1. School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Christopher M. Kirkham, James N. Scott & Joan Boyes

  2. School of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Sarah Bevington

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  3. Joan Boyes
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  4. Sarah Bevington
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Correspondence to Sarah Bevington .

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Editors and Affiliations

  1. Institute of Biomedical Research, University of Birmingham Medical and Dental Sciences, Birmingham, United Kingdom

    Constanze Bonifer

  2. Institute of Biomedical Research, University of Birmingham Medical and Dental Sciences, Birmingham, United Kingdom

    Peter N. Cockerill

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© 2014 Springer-Verlag Berlin Heidelberg

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Kirkham, C.M., Scott, J.N., Boyes, J., Bevington, S. (2014). The Molecular Basis of B Cell Development and the Role of Deregulated Transcription and Epigenetics in Leukaemia and Lymphoma. In: Bonifer, C., Cockerill, P. (eds) Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45198-0_13

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