Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

SIMPLE SUMMARY: B-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. ABSTRACT: 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.