Regulation of Human ERV in Lymphoma by Epigenetic Modifying Agents
Open AccessThe lymphatic system is a subset of the immune system, a multifaceted organization that has responsibilities ranging from protecting the body from invaders and removing cellular waste to maintaining body fluid levels and absorbing dietary fat from our intestines. More notably, it’s responsible for the white blood cells our body uses to fight infection and keep ourselves healthy. There are several types of cancers that can impact the functioning of this system, divided into Hodgkin’s and non-Hodgkin’s lymphomas. Mantle cell lymphoma, a rare aggressive subtype of NHL, occurs in the mantle zone of lymphatic nodules. By the time the presence of NHL is detected, it often has already metastasized, complicating treatment, and negatively affecting the patient’s prognosis. Current treatment options consist of both traditional chemotherapies and non-chemotherapeutic options but still fall short of desired patient outcomes. As novel therapies are required, it is time to look elsewhere.An emerging field of study, epigenomics, may hold the key. Epigenomics is the study of genetic regulation and the changes in gene expression that can have profound influences on an organism’s phenotype. Without changing the actual genetic code, the expression of certain genes can be tuned up and down either by external or internal factors. Often, though, these influences come from within. Most of the human genome does not code directly for amino acids, rather, much of it subtly influences the expression of sections that do. Some of these non-coding regions are sections of DNA that we’ve accumulated through evolution over millions of years or are otherwise left over from our ancestors. Other sections include the induction of DNA and RNA from ancient retroviruses that have slowly integrated into our own genome. These sections of our genome, those that are the result of ancient exogenous retroviruses, are colloquially known as endogenous retroviruses, or ERVs. Human endogenous retroviruses, HERVs, are thought to play a significant role in genetic regulation. In recent years, scientists have been able to link the abnormal regulation of some of these HERVs to several types of cancer ranging from colorectal to pancreatic. Given these findings, it is pertinent to investigate whether these genetic sections may also be linked to mantle cell lymphoma, as the potential correlation is not yet well known. Epigenetic medications, those that aid in the external up or down-regulation of genetic transcription, may serve to be a point of leverage in the fight against adverse patient outcomes. Should a concerning link be found between a HERV and a type of malignancy, these epigenetic drugs may serve to address these concerns. As this broad class of epigenetic drugs function through different mechanisms, we opted to test a variety of different subclasses to examine their effect on our target ERVs. In this study, we hope to scout for any potential correlations between abnormal HERV expression and NHL development and examine the effects of several epigenetic drugs on our target HERVs.
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