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

IF 2.5 Q3 ONCOLOGY
Athena Dong, Yi-Wen Huang, Ben Niu, Ruiling Liu, Weijie Wu, Haiyan Gao, Jianhua Yu, Li-Shu Wang
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引用次数: 0

摘要

骨髓增生异常综合征(MDS)是骨髓恶性肿瘤的一个亚型,其定义是未成熟造血干细胞的克隆性导致血细胞发育不良。这些综合征可导致感染风险增加,并可能转化为急性髓系白血病,因此确定有效的治疗方法至关重要。虽然阿扎胞苷和地西他滨等低甲基化药物以及干细胞移植已被确定为 MDS 的首选治疗方法,但并非所有患者在生理上都能接受这些治疗。然而,黑树莓(BRB)已被证明在各种恶性肿瘤中具有低甲基化作用,且不良反应极小,因此具有更广泛的潜在适应症。本研究旨在利用性梳样添加物/甲基胞嘧啶二氧合酶2(Asxl1/Tet2)双基因敲除小鼠(Vav-cre Asxl1fl/fl Tet2fl/fl)研究BRB对MDS产生这种影响的潜力。在对 Vav-cre Asxl1fl/fl Tet2fl/fl 小鼠进行为期 12 周的 5%BRBs饮食补充后,我们观察到多个转录起始位点和与造血等关键通路相关的基因内位置都出现了高甲基化和低甲基化现象。这种甲基化特征可能对延缓 MDS 的发病有影响,因此需要进行深入研究。我们的研究结果强调了探索延长BRB干预是否能有效改变MDS风险并阐明BRB诱导的甲基化变化之间关系的重要性,从而进一步揭示BRB对MDS患者的潜在益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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-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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