The bromodomain and extra-terminal(BET)proteins act as“readers”for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes.BET protein is associated with transcriptional elongation ...The bromodomain and extra-terminal(BET)proteins act as“readers”for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes.BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2,and is involved in the regulation of cell cycle and apoptosis.Meanwhile,BET inhibitors(BETi)have regulatory effects on immune checkpoints,immune cells,and cytokine expression.The role of BET proteins and BETi in a variety of tumors has been studied.This paper reviews the recent research progress of BET and BETi in hematologic tumors(mainly leukemia,lymphoma and multiple myeloma)from cellular level studies,animal studies,clinical trials,drug combination,etc.BETi has a promising future in hematologic tumors,and future research directions may focus on the combination with other drugs to improve the efficacy.展开更多
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 ...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.展开更多
基金supported by grants from Cuiying Technology Innovation Project of Lanzhou University Second Hospital(China)(No.CY2017-ZD04 and CY2019-MS14)Commissioned Project of National Clinical Medicine Research Center for Hematological System Diseases(China)(No.2021WWA01)Talent Innovation and Entrepreneurship Project of Lanzhou,China(No.2020-RC-48).
文摘The bromodomain and extra-terminal(BET)proteins act as“readers”for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes.BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2,and is involved in the regulation of cell cycle and apoptosis.Meanwhile,BET inhibitors(BETi)have regulatory effects on immune checkpoints,immune cells,and cytokine expression.The role of BET proteins and BETi in a variety of tumors has been studied.This paper reviews the recent research progress of BET and BETi in hematologic tumors(mainly leukemia,lymphoma and multiple myeloma)from cellular level studies,animal studies,clinical trials,drug combination,etc.BETi has a promising future in hematologic tumors,and future research directions may focus on the combination with other drugs to improve the efficacy.
文摘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.
