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Aberrant Epigenomic Regulatory Networks in Multiple Myeloma and Strategies for Their Targeted Reversal

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The DNA, RNA, and Histone Methylomes

Part of the book series: RNA Technologies ((RNATECHN))

Abstract

Multiple Myeloma (MM), a subset of genetically complex paraproteinaemias, is characterized by abnormal clonal plasma cell expansion in the bone marrow, and accounts for about 13% of all patients with hematological malignancies. Primary genomic abnormalities include IgH translocations to MMSET/FGFR3 (4p16), CCND1 (11q13), MAF (16q23), or MAFB (20q12), as well as aneuploidy involving trisomies of several chromosomes, known as hyperdiploidy, and together are the hallmarks of the disease. Besides these structural abnormalities, recurrent mutations affecting key oncogenes and tumor suppressor genes are found, as well as aberrant modifications in epigenetic marks which deregulate key oncogenes in MM. Herein, we undertake to review the global epigenetic regulatory landscape of MM including DNA methylation, histone modifications, non-coding miRNA mechanisms or interactions from regulatory proteins such as CTCF and super-enhancers (SE), in conjunction with gene expression and function in MM molecular subgroups at different stages of disease progression. Additionally, we discuss new perspectives in designing CRISPR/TAL-based synthetic proteins or novel small molecular drugs to target aberrant epigenetic marks with locus-specific precision, which may be an option for therapeutic intervention.

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Authors and Affiliations

  1. Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Samrat Roy Choudhury & Brian A. Walker

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  1. Samrat Roy Choudhury
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  1. Nanobiomedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  2. Nanobiomedical Center, Adam Mickiewicz University, Poznań, Poland

    Jan Barciszewski

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Roy Choudhury, S., Walker, B.A. (2019). Aberrant Epigenomic Regulatory Networks in Multiple Myeloma and Strategies for Their Targeted Reversal. In: Jurga, S., Barciszewski, J. (eds) The DNA, RNA, and Histone Methylomes. RNA Technologies. Springer, Cham. https://doi.org/10.1007/978-3-030-14792-1_22

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