在AML患者中DNA甲基化模式的预测值,这些患者接受了含阿扎西提丁的诱导治疗方案
Maximilian Schmutz1,2, Manuela Zucknick2,3, Richard F Schlenk4,5
1Hematology and Oncology, Medical Faculty, University of Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.
Clinical epigenetics
|October 27, 2023
概括
使用DNA甲基化配置文件预测急性髓性白血病 (AML) 治疗反应是具有挑战性的. 全基因组甲基化模式,局限于特定区域而不是单个CpG,显示出可能从低甲基化剂 (HMA) 中受益的患者的识别潜力.
科学领域:
- 表观遗传学和基因组学
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 急性髓性白血病 (AML) 是一种复杂的血液癌症,预后不佳.
- 表观遗传失调,特别是DNA甲基化,在AML的发展中起着关键作用.
- 目前针对AML的低甲基化剂 (HMA) 疗法缺乏治疗反应的预测生物标志物.
研究的目的:
- 调查是否治疗前全基因组DNA甲基化概况可以预测AML患者接受阿扎西提丁基导诱导疗法的缓解.
- 评估不偏的甲基-CpG选试验的价值,以确定信息化甲基化变化.
- 为了比较基因组区域与单个CpG对治疗反应的预测能力.
主要方法:
- 从155名新诊断的AML患者使用甲基-CpG免疫沉-seq.q.的DNA甲基化资料的分析.
- 识别差异甲基化区域 (DMR) 和训练使用惩罚后勤回归的预测分类器.
- 使用定量甲基化分析和质谱法 (MALDI-TOF) 验证甲基化区域和分类器性能.
主要成果:
- 确定了1755个差异甲基化区域 (DMR),包括与WNT10A和GATA3.3相关的区域.
- 一个12-CpG分类器证明了对阿扎西提丁反应的AUC为0.77的预测能力.
- 预测准确性在非阿扎西丁组 (AUC 0.76) 中保持不变,这表明预测能力更广泛.
结论:
- 全基因组甲基化查可以识别信息变化,用于预测AML治疗反应.
- 预测性表观型的特征是复杂的全基因组甲基化模式,仅限于特定区域,而不是孤立的CpG.
- 确定的DMR与关键的瘤转化过程有关,支持它们的生物相关性.
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