Athena Dong, Yi-Wen Huang, Ben Niu, Ruiling Liu, Weijie Wu, Haiyan Gao, Jianhua Yu, Li-Shu Wang
{"title":"补充黑树莓对骨髓增生异常综合征早期 Vav-creAsxl1fl/flTet2fl/fl 双基因敲除小鼠甲基化途径的影响","authors":"Athena Dong, Yi-Wen Huang, Ben Niu, Ruiling Liu, Weijie Wu, Haiyan Gao, Jianhua Yu, Li-Shu Wang","doi":"10.15430/JCP.2023.28.4.212","DOIUrl":null,"url":null,"abstract":"<p><p>Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using <i>Addition of Sex Combs Like</i>/<i>Tet Methylcytosine Dioxygenase 2</i> (<i>Asxl1</i>/<i>Tet2</i>) double knockout mice (<i>Vav-cre</i> <i>Asxl1</i><sup><i>fl/fl</i></sup> <i>Tet2</i><sup><i>fl/fl</i></sup>), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of <i>Vav-cre</i> <i>Asxl1</i><sup><i>fl/fl</i></sup> <i>Tet2</i><sup><i>fl/fl</i></sup> mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774484/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of Black Raspberry Supplementation on Methylation Pathways in <i>Vav-cre</i><i>Asxl1</i><sup><i>fl/fl</i></sup><i>Tet2</i><sup><i>fl/fl</i></sup> Double Knockout Mice with Early-stage Myelodysplastic Syndrome.\",\"authors\":\"Athena Dong, Yi-Wen Huang, Ben Niu, Ruiling Liu, Weijie Wu, Haiyan Gao, Jianhua Yu, Li-Shu Wang\",\"doi\":\"10.15430/JCP.2023.28.4.212\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using <i>Addition of Sex Combs Like</i>/<i>Tet Methylcytosine Dioxygenase 2</i> (<i>Asxl1</i>/<i>Tet2</i>) double knockout mice (<i>Vav-cre</i> <i>Asxl1</i><sup><i>fl/fl</i></sup> <i>Tet2</i><sup><i>fl/fl</i></sup>), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of <i>Vav-cre</i> <i>Asxl1</i><sup><i>fl/fl</i></sup> <i>Tet2</i><sup><i>fl/fl</i></sup> mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.</p>\",\"PeriodicalId\":15120,\"journal\":{\"name\":\"Journal of Cancer Prevention\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774484/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cancer Prevention\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15430/JCP.2023.28.4.212\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer Prevention","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15430/JCP.2023.28.4.212","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Effects of Black Raspberry Supplementation on Methylation Pathways in Vav-creAsxl1fl/flTet2fl/fl Double Knockout Mice with Early-stage Myelodysplastic Syndrome.
Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-creAsxl1fl/flTet2fl/fl), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-creAsxl1fl/flTet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.