Dear Editor,The t(8;21)(q22;q22) translocation is a common chromosomal abnormality in acute myeloid leukemia (AML). Although t(8;21) AML has a favorable prognosis, ~40% of the patients will eventually relapse [1, 2]. Even with allogeneic hematopoietic stem cell transplantation (allo-HSCT), ~20% of patients still relapse, and further treatment is limited [3].

亲爱的编辑，t（8；21）（q22；q22）易位是急性髓性白血病（AML）中常见的染色体异常。尽管t（8；21）AML预后良好，但约40%的患者最终会复发[1，2]。即使使用异基因造血干细胞移植（allo-HSCT），仍有约20%的患者复发，进一步的治疗受到限制（3）。

Notably, KIThigh mutation, particularly the KIT-D816 mutation, as well as FLT3-ITDhigh alterations, have been reported to confer poor prognosis in t(8;21) AML patients, although there remains controversy [4,5,6,7]. Other factors like aberrant immunophenotype, high white blood cell (WBC) counts, and high measurable residual disease (MRD) levels evaluated by multiparameter flow cytometry (MFC) also indicate worse outcomes [8, 9].

值得注意的是，据报道，Kithhigh突变，特别是KIT-D816突变，以及FLT3 ITDhigh改变，在t（8；21）AML患者中预后不良，尽管仍存在争议[4,5,6,7]。通过多参数流式细胞术（MFC）评估的异常免疫表型，高白细胞（WBC）计数和高可测量残留疾病（MRD）水平等其他因素也表明预后较差[8，9]。

However, these do not fully illuminate the molecular or clinical variations observed in t(8;21) AML. Therefore, it is crucial to improve current risk stratification and identify those with a high risk of relapse as early as possible for tailored treatment strategies.To elucidate the expression profile and molecular characteristics of t(8;21) AML, we incorporated transcriptome data and clinical information from 42 t(8;21) AML patients at diagnosis administered in our center between September 2020 and October 2022 (Supplemental Table 1).

然而，这些并不能完全阐明在t（8；21）AML中观察到的分子或临床变异。因此，至关重要的是要改善目前的风险分层，并尽早确定复发风险高的患者，以制定量身定制的治疗策略。为了阐明t（8；21）AML的表达谱和分子特征，我们纳入了2020年9月至2022年10月期间在我们中心进行诊断的42例t（8；21）AML患者的转录组数据和临床信息（补充表1）。

Using non-negative matrix factorization followed by consensus-clustering analysis (Supplementary Methods), three distinct transcriptional subgroups were identified based on 240 genes, named cluster 1 (C1) (38.1%, 16/42), cluster 2 (C2) (35.7%, 15/42), and cluster 3 (C3) (26.2%, 11/42), respectively (Fig.

使用非负矩阵分解，然后进行共识聚类分析（补充方法），基于240个基因鉴定了三个不同的转录亚组，分别命名为簇1（C1）（38.1%，16/42），簇2（C2）（35.7%，15/42）和簇3（C3）（26.2%，11/42）（图。

1A, Supplemental Table 2). C1 was characterized by abnormal expression of leukemia stem and progenitor signatures (Fig. 1B). C2 and C3 were both enriched for i.

1A，补充表2）。C1的特征是白血病干细胞和祖细胞特征的异常表达（图1B）。C2和C3都富含i。

Data availability

数据可用性

The HOVON AML cohort [11] was retrieved from Array Express (Dataset ID: E-MTAB-3444). Other datasets supporting this study are not publicly available due to ethics considerations and privacy restrictions but can be requested from the corresponding author upon reasonable request.

HOVON AML队列（11）是从Array Express（数据集ID：E-MTAB-3444）中检索到的。由于道德考虑和隐私限制，支持这项研究的其他数据集尚未公开，但可以在合理要求下向通讯作者索取。

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Download referencesFundingThis work was supported by National Key Research and Development Program of China (2021YFC2500300), National Natural Science Foundation of China (82341213, 82000131), CAMS Innovation Fund for Medical Sciences (2021-I2M-1-041), Clinical Research Foundation of National Clinical Research Center for Blood Diseases (2023NCRCA0101), Tianjin Municipal Science and Technology Commission Grant (23JCYBJC01050).Author informationAuthor notesThese authors contributed equally: Yu Liu, Wenbing Liu, Anli Lai.Authors and AffiliationsState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, ChinaYu Liu, Wenbing Liu, Anli Lai, Yihan Mei, Ying Wang, Hui Wei, Qing Rao, Runxia Gu, Yingchang Mi, Min Wang, Jianxiang Wang & Shaowei QiuTianjin Institutes of Health Science, Tianjin, 301600, ChinaYu Liu, Wenbing Liu, Anli Lai, Yihan Mei, Ying Wang, Hui Wei, Qing Rao, Runxia Gu, Yingchang Mi, Min Wang, Jianxiang Wang & Shaowei QiuAuthorsYu LiuView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了国家重点研究发展计划（2021YFC2500300），国家自然科学基金（823412138200131），CAMS医学科学创新基金（2021-I2M-1-041），国家血液疾病临床研究中心临床研究基金（2023NCRCA0101），天津市科学技术委员会资助（23JCYBJC01050）的支持。作者信息作者注意到这些作者做出了同样的贡献：刘宇，刘文兵，赖安丽。作者和单位国家血液病临床研究中心实验血液学国家重点实验室，中国医学科学院和北京协和医学院血液与血液病研究所海河细胞生态实验室，天津，300020，刘国宇，刘文兵，赖安丽，梅一汉，王英，魏辉，饶青，顾润霞，米英昌，王敏，王建祥，邵伟邱天津卫生科学研究院，301600，刘国宇，刘文兵，赖安丽，梅一汉，王英，魏辉，饶青，顾润霞，米英昌，王敏，王建祥＆Shaowei QiuAuthorsYu LiuView作者出版物您也可以在中搜索此作者。

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PubMed Google ScholarContributionsJW and SQ conceptualized the research project. YL, WL, AL, YM, and QR collected and analyzed the data. JW, SQ, YM, HW, YW, and RG managed patients and provided clinical data. YL wrote the original draft. SQ, MW, and JW reviewed the manuscript.

PubMed Google ScholarContributionsJW和SQ将研究项目概念化。YL，WL，AL，YM和QR收集并分析了数据。JW，SQ，YM，HW，YW和RG管理患者并提供临床数据。YL写了原稿。。

All authors have full access to all the data in the study and are ultimately responsible for the decision to submit for publication.Corresponding authorsCorrespondence to.

所有作者都可以完全访问研究中的所有数据，并最终对提交出版物的决定负责。通讯作者通讯。

Jianxiang Wang or Shaowei Qiu.Ethics declarations

。道德宣言

Competing interests

相互竞争的利益

JW: Advisor for AbbVie. The remaining authors declare no competing interests.

JW：AbbVie的顾问。其余作者声明没有利益冲突。

Ethics

伦理学

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of the Institute of Hematology and Blood Diseases Hospital (Ref: NKRDP2021005-EC-2). Informed consent was obtained from all patients.

这项研究是根据赫尔辛基宣言的指导方针进行的，并得到了血液学和血液病医院研究所机构审查委员会的批准（参考文献：NKRDP2021005-EC-2）。所有患者均获得知情同意。

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Reprints and permissionsAbout this articleCite this articleLiu, Y., Liu, W., Lai, A. et al. Multiomic analysis identifies a high-risk subgroup that predicts poor prognosis in t(8;21) acute myeloid leukemia.

转载和许可本文引用本文Liu，Y.，Liu，W.，Lai，A。等人。多组学分析确定了一个预测t（8；21）急性髓细胞白血病预后不良的高危亚组。

Blood Cancer J. 14, 162 (2024). https://doi.org/10.1038/s41408-024-01144-1Download citationReceived: 03 July 2024Revised: 30 August 2024Accepted: 05 September 2024Published: 16 September 2024DOI: https://doi.org/10.1038/s41408-024-01144-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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