急性髓性白血病的染色质景观和表观遗传异质性，这一成果由京都大学Seishi Ogawa研究团队经过不懈努力而取得。2026年7月8日出版的《自然》发表了这项成果。

在这里，该课题组人员对1,563名最近诊断为AML的个体（“eCHROMA”队列）进行了ATAC-seq（通过测序检测转座酶可及的染色质），以显示AML可以根据染色质可及性特征分为16个亚组。基因突变、转录组、DNA甲基化和组蛋白标记的多组学分析表明，这些ATAC亚群表现出不同的驱动突变、分化状态、基因表达、DNA甲基化和超增强子谱，并且还与临床结果相关。

这些发现在独立队列中得到了验证。单细胞ATAC测序显示，每个亚组中的所有白血病细胞都具有共同的染色质可接近性，这表明亚组特异性表观基因组指纹是基于ATAC分类的基础。从机制上讲，亚群具有独特的基因调控网络，这些基因调控网络由造血过程中关键转录因子的活性驱动，并且亚群特异性超增强子在其中起着关键作用。多组学单细胞分析进一步揭示了与染色质可及性和基因表达相关的不受调控的分化轨迹。

值得注意的是，与基因组分类相比，ATAC亚组具有独立的预后作用，并且与特定的药物敏感性相关。总之，基于ATAC的染色质谱分析，结合多组学数据，提供了超越基因组学的AML发病机制的见解，并为AML研究提供了有价值的抵抗。

据了解，急性髓性白血病（AML）是一种侵袭性血癌，其特征是未成熟的髓母细胞增殖不受调节。基因突变已被证明对AML的发病机制、肿瘤间异质性和临床结果有很大影响；然而，表观遗传改变在这些方面的作用研究较少。

附：英文原文

Title: Chromatin landscape and epigenetic heterogeneity of acute myeloid leukaemia

Author: Ochi, Yotaro, Liew-Littorin, Markus, Nannya, Yasuhito, Bengtzen, Sofia, Piauger, Benedicte, Deneberg, Stefan, Jdersten, Martin, Lazarevic, Vladimir, Cammenga, Jrg, Robelius, Anna, Wennstrm, Lovisa, lander, Emma, Kasahara, Senji, Hiramoto, Nobuhiro, Kanemura, Nobuhiro, Sezaki, Nobuo, Sakurada, Maki, Iwasaki, Makoto, Kanda, Junya, Ueda, Yasunori, Yoshihara, Satoshi, Erkers, Tom, Struyf, Nona, Watanabe, Yu, Motomura, Masanori, Nakagawa, Masahiro M., Saiki, Ryunosuke, Fukushima, Hidehito, Okazaki, Koji, Morimoto, Suguru, Yoda, Akinori, Okuda, Rurika, Komatsu, Shintaro, Xie, Guoxiang, sterroos, Albin, Kon, Ayana, Zhao, Lanying, Shiraishi, Yuichi, Ishikawa, Takayuki, Miyano, Satoru, Katayama, Kotoe, Imoto, Seiya, Matsuda, Shuichi, Takaori-Kondo, Akifumi, Aburatani, Hiroyuki, Suzuki, Hiroshi I., Kallioniemi, Olli, Juliusson, Gunnar, Hglund, Martin, Lehmann, Sren, Ogawa, Seishi

Issue&Volume: 2026-07-08

Abstract: Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by the unregulated proliferation of immature myeloblasts. Gene mutations have been shown to have a large effect on pathogenesis, inter-tumour heterogeneity and clinical outcomes in AML1,2,3,4,5,6,7,8; however, the role of epigenetic alterations in these respects has been investigated less extensively. Here we use ATAC-seq (assay for transposase-accessible chromatin with sequencing) in a cohort of 1,563 individuals with a recent diagnosis of AML (the ‘eCHROMA’ cohort) to show that AML can be classified into 16 subgroups on the basis of chromatin accessibility profiles. Multiomics analyses of gene mutations, the transcriptome, DNA methylation and histone marks show that these ATAC subgroups exhibit distinct driver mutations, differentiation states, gene expression, DNA methylation and super-enhancer profiles, and are also associated with clinical outcomes. These findings were validated in independent cohorts. Single-cell ATAC sequencing reveals that all leukaemic cells in each subgroup share a common chromatin accessibility profile, which suggests that subgroup-specific epigenomic fingerprints underlie the ATAC-based classification. Mechanistically, the subgroups have distinct gene-regulatory networks that are driven by the activities of key transcription factors in haematopoiesis, and in which subgroup-specific super-enhancers have a pivotal role. Multiomics single-cell analysis further reveals deregulated trajectories of differentiation coupled with chromatin accessibility and gene expression. Notably, ATAC subgroups have an independent prognostic effect, compared with genomic classification, and are associated with particular drug sensitivities. In summary, ATAC-based chromatin profiling, combined with multiomics data, provides insights into AML pathogenesis beyond genomics and constitutes a valuable resource for AML research.

DOI: 10.1038/s41586-026-10703-4

Source: https://www.nature.com/articles/s41586-026-10703-4