Sam Humphries, Danielle R Bond, Zacary P Germon, Simon Keely, Anoop K Enjeti, Matthew D Dun, Heather J Lee
{"title":"急性髓细胞白血病中DNA甲基化与缺氧之间的串扰。","authors":"Sam Humphries, Danielle R Bond, Zacary P Germon, Simon Keely, Anoop K Enjeti, Matthew D Dun, Heather J Lee","doi":"10.1186/s13148-023-01566-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.</p><p><strong>Main body: </strong>This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.</p><p><strong>Conclusion: </strong>Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500762/pdf/","citationCount":"0","resultStr":"{\"title\":\"Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.\",\"authors\":\"Sam Humphries, Danielle R Bond, Zacary P Germon, Simon Keely, Anoop K Enjeti, Matthew D Dun, Heather J Lee\",\"doi\":\"10.1186/s13148-023-01566-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.</p><p><strong>Main body: </strong>This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.</p><p><strong>Conclusion: </strong>Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.</p>\",\"PeriodicalId\":48652,\"journal\":{\"name\":\"Clinical Epigenetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2023-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500762/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Epigenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13148-023-01566-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-023-01566-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.
Background: Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.
Main body: This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.
Conclusion: Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.
Clinical EpigeneticsBiochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.