Abstract
Simple SummaryB-cell malignancies are a heterogenous group of lymphomas and leukemias and are the 6th most common cancer-related cause of death. Apart from several oncogenes and tumor suppressors involved in their pathogenesis, recently the role of non-coding, regulatory sequences has been implied. Enhancers are DNA elements controlling gene expression to ensure proper cell development and function. However, the activity of enhancers can be redirected, setting cells on the path towards cancer. In this review, we discuss different mechanisms through which enhancers are exploited in malignant B cells. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation.B-cell lymphomas and leukemias derive from B cells at various stages of maturation and are the 6th most common cancer-related cause of death. While the role of several oncogenes and tumor suppressors in the pathogenesis of B-cell neoplasms was established, recent research indicated the involvement of non-coding, regulatory sequences. Enhancers are DNA elements controlling gene expression in a cell type- and developmental stage-specific manner. They ensure proper differentiation and maturation of B cells, resulting in production of high affinity antibodies. However, the activity of enhancers can be redirected, setting B cells on the path towards cancer. In this review we discuss different mechanisms through which enhancers are exploited in malignant B cells, from the well-studied translocations juxtaposing oncogenes to immunoglobulin loci, through enhancer dysregulation by sequence variants and mutations, to enhancer hijacking by viruses. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation.
Highlights
B-cell malignancies are a diverse group of blood cancers which include several types of leukemias and lymphomas: Hodgkin’s lymphoma and non-Hodgkin lymphomas [1,2,3]
Recent advances clearly indicate that the non-coding, regulatory parts of the genome are critically involved in cancer pathogenesis
He we presented an overview of the role of enhancers in B-cell malignancies
Summary
B-cell malignancies are a diverse group of blood cancers which include several types of leukemias and lymphomas: Hodgkin’s lymphoma and non-Hodgkin lymphomas [1,2,3] They originate from B cells at different developmental stages [4]. Enhancers are regulatory DNA elements with a pivotal role in shaping cell type-specific transcriptional programs in response to intra- and extracellular signals [11] They contain sequences recognized by transcription factors and serve as platforms for assembly of an enhanceosome [12]—a multi-protein complex, able to recruit chromatin remodelers and RNA polymerase at the promoter region of target gene, and eventually lead to its expression. In mature B cells, antigen-dependent activation triggers somatic hypermutation (SHM) during the germinal center reaction This leads to further diversification of the variable region of IGH and allows selection of B cells with high affinity B-cell receptor. The IGH locus contains two enhancers that govern its activity: Eμ and 3 regulatory region (3 RR)
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