J Cancer Prev.
2023 Dec;28(4):212-218. 10.15430/JCP.2023.28.4.212.
Effects of Black Raspberry Supplementation on Methylation Pathways in Vav-cre Asxl1 fl/fl Tet2 fl/fl Double Knockout Mice with Early-stage Myelodysplastic Syndrome
- Affiliations
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- 1Medical School, Medical College of Wisconsin, WI, USA
- 2Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
- 3State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory of Post-Harvest Fruit Processing, Key Laboratory of Post-Harvest Vegetable Preservation and Processing (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Key Laboratory of Fruit and Vegetable Preservation and Processing Technology of Zhejiang Province, Key Laboratory of Light Industry Fruit and Vegetable Preservation and Processing, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
- 4Department of Hematology and Hematopoietic Cell Transplantation, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA, USA
- KMID: 2550705
- DOI: http://doi.org/10.15430/JCP.2023.28.4.212
Abstract
- 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-cre Asxl1fl/fl Tet2fl/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-cre Asxl1fl/fl Tet2fl/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.
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