LEP启动子甲基化在未确定意义的克隆性细胞减少症和骨髓增生异常综合征的发生和进展中的作用。

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-05-26 DOI:10.1186/s13148-023-01505-w
Katja Kaastrup, Linn Gillberg, Stine U Mikkelsen, Andreas D Ørskov, Claudia Schöllkopf, Bo K Mortensen, Bo Porse, Jakob W Hansen, Kirsten Grønbæk
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引用次数: 0

摘要

背景:特发性非克隆性细胞减少症(ICUS)和克隆性细胞减少症(CCUS)在老年人群中很常见。虽然这些实体具有相似的临床表现,外周血细胞减少和不到10%的骨髓异常增生,但它们的恶性潜能不同,这些疾病与骨髓增生异常综合征(MDS)等髓系肿瘤之间的生物学关系尚不完全清楚。异常DNA甲基化在MDS和急性髓性白血病(AML)发病机制中起着至关重要的作用。此外,肥胖导致MDS患者预后较差,总生存率较低,AML转化率较高。在这项研究中,我们测量了来自ICUS、CCUS和MDS患者以及健康对照者的造血细胞中肥胖调节基因LEP(编码瘦素)启动子的DNA甲基化。我们研究了LEP启动子甲基化是否是髓系肿瘤发展的早期事件,以及它是否与临床结果相关。结果:我们发现,与健康对照组相比,icu、CCUS和MDS患者的血细胞中LEP启动子都有显著的高甲基化,LEP高甲基化与贫血、骨髓母细胞百分比增加和血浆瘦素水平降低有关。LEP启动子甲基化高的MDS患者有更高的进展风险、更短的无进展生存期和更低的总生存期。此外,在多变量Cox回归分析中,LEP启动子甲基化是MDS进展的独立危险因素。结论:总之,LEP启动子的高甲基化在髓系肿瘤中是一个早期和频繁的事件,并与较差的预后相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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LEP promoter methylation in the initiation and progression of clonal cytopenia of undetermined significance and myelodysplastic syndrome.

Background: Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome.

Results: We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis.

Conclusion: In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, 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.
期刊最新文献
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