Kimura Shunsuke
Department of Pediatrics, The University of Tokyo.
Department of Pediatrics, Hiroshima University.
Rinsho Ketsueki. 2019;60(5):459-467. doi: 10.11406/rinketsu.60.459.
Recent development of massive parallel-sequencing technology has revealed the genetic basis of pediatric T-cell acute lymphoblastic leukemia (T-ALL). However, epigenetic profiles of T-ALL, such as DNA methylation, have not been well characterized. To describe the epigenetic landscape of T-ALL, we investigated DNA methylation profiles of 79 cases with pediatric T-ALL by using the EPIC methylation array, which allowed us to perform more profound analyses, including the OpenSea region. Moreover, we conducted combined analyses of methylation data using our previous expression and mutation data. Based on DNA methylation profiles, pediatric T-ALL was clustered into four distinct subtypes, which exhibited remarkable association with genetic signatures and expression features, as well as profiles of normal T-cell development. Furthermore, our study revealed the importance of methylation status at binding sites of polycomb-repressive complex components and transcription factors, such as SPI1, in the classification of pediatric T-ALL based on DNA methylation status. These results might be helpful in the development of new therapeutic strategies for pediatric T-ALL.
大规模平行测序技术的最新进展揭示了儿童T细胞急性淋巴细胞白血病（T-ALL）的遗传基础。然而，T-ALL的表观遗传特征，如DNA甲基化，尚未得到充分表征。为了描述T-ALL的表观遗传格局，我们使用EPIC甲基化芯片研究了79例儿童T-ALL病例的DNA甲基化谱，这使我们能够进行更深入的分析，包括OpenSea区域。此外，我们结合之前的表达和突变数据对甲基化数据进行了联合分析。基于DNA甲基化谱，儿童T-ALL被聚类为四个不同的亚型，这些亚型与遗传特征、表达特征以及正常T细胞发育谱显著相关。此外，我们的研究揭示了多梳抑制复合物成分和转录因子（如SPI1）结合位点的甲基化状态在基于DNA甲基化状态的儿童T-ALL分类中的重要性。这些结果可能有助于开发针对儿童T-ALL的新治疗策略。
