Enhancer Deregulation in Myeloma

The complexity of gene expression regulation is the result of a composite interplay between promoters, enhancers and other cis-acting regulatory elements bound by transcription factors (TFs) that controls the transcriptional activity of genes. Primary tumor cells, in comparison to their healthy counterparts, are known to display altered enhancer repertoires that are associated with tumor-specific transcription. Large groups of transcriptional enhancers cluster together to form super-enhancers (SEs). These elements have been shown to control genes that are important for maintaining cell identity but are also frequently associated with oncogenes as well as translocations that result in aberrant gene expression in cancer. Immunoglobulin (IGH, IGL, IGK) and non-immunoglobulin (PVT1, FAM46C, DUSP22, etc.) enhancers hijacking by variable genes (MYC, MAF, CCND1/2/3, MMSET, IRF4) is a recognized oncogenic driver event in multiple myeloma (MM). However, the identity of the TFs or transcriptional regulatory complexes binding and regulating the activity of these enhancers remains to be fully elucidated and may yield valuable therapeutic targets. In this regard, the bromodomain and extra-terminal (BET) inhibitors have emerged as promising molecules for the treatment of hematologic malignancies. BET family proteins are chromatin adaptors, functionally linked to important pathways for cellular viability and cancer signaling. In particular, BRD4 has a direct role in the transcription regula...
Source: Blood - Category: Hematology Authors: Tags: Targeting Epigenetic Regulation in Myeloma Source Type: research