Human Endogenous Retroviruses and Hematological Malignant Tumors

Abstract Human endogenous retrovirus (HERV) gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes, accounting for approximately 8%–9% of the human genome. Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts, mutations, and sequence deletions or insertions over the millions of years, but their expression is highly regulated by epigenetic and host defense mechanisms. However, there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure. The abnormal activation of HERVs may contribute to diseases or their pathology, such as malignant tumors, autoimmune diseases, and nervous system diseases. The occurrence and development of hematological malignant tumors (HMTs) is a complex process involving interactions of multiple genetic and environmental factors. The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms. In this review, we address the discovery of endogenous retroviruses in vertebrates, and the classification and genomic structure of HERVs. Among HERV family members, HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity. We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches. However, much remains to be learned about not only the impact of HERVs on the occurrence of HMTs, but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.