Dear Editor,Approximately 25–35% of adult patients with acute myeloid leukemia (AML) carries NPM1 mutation, which generally indicated a favorable outcome in the absence of FLT3-ITD mutation [1]. NPM1 mutations are absent in clonal hematopoiesis, and have been considered as AML initiating lesions [2].

亲爱的编辑，大约25-35%的成人急性髓细胞白血病（AML）患者携带NPM1突变，这通常表明在没有FLT3-ITD突变的情况下预后良好[1]。NPM1突变在克隆造血中不存在，被认为是AML起始病变（2）。

Research on co-mutation characteristics of NPM1-mutated patients concentrated on FLT3-ITD, which has been suggested to hold a negative prognostic impact on NPM1-mutated patients by several large retrospective clinical studies [3, 4]. Besides FLT3-ITD, although there remains controversy, other high-frequency co-mutations such as DNMT3A, IDH1, IDH2, FLT3-TKD, NRAS, and WT1 mutations have also been pointed out to affect the prognosis of NPM1-mutated patients [3, 5,6,7,8,9].

NPM1突变患者共突变特征的研究集中在FLT3-ITD上，几项大型回顾性临床研究表明，这对NPM1突变患者的预后有负面影响[3，4]。除FLT3-ITD外，尽管仍存在争议，但其他高频共突变如DNMT3A，IDH1，IDH2，FLT3-TKD，NRAS和WT1突变也被指出会影响NPM1突变患者的预后[3,5,6,7,8,9]。

Indeed, identification of specific co-mutation combinations other than FLT3-ITD mutation is essential for precise risk stratification and treatment strategy optimization for NPM1-mutated AML patients. Since allogeneic hematopoietic stem cell transplantation (allo-HSCT) is generally considered to improve the long-term outcome of most adverse-risk and suitable intermediate-risk AML patients, for NPM1-mutated AML patients, it is imperative to revisit the co-mutation profiles to determine the optimal population who may benefit from allo-HSCT.In this study, we conducted a retrospective analysis of newly diagnosed adult AML patients with NPM1 mutations (acute promyelocytic leukemia excluded) in our center diagnosed from October 2018 to December 2022, focusing on exploring the therapeutic and prognostic significance of co-mutation characteristics in AML patients with NPM1 mutations.

实际上，鉴定FLT3-ITD突变以外的特定共突变组合对于NPM1突变的AML患者的精确风险分层和治疗策略优化至关重要。由于异基因造血干细胞移植（allo-HSCT）通常被认为可以改善大多数不良风险和合适的中等风险AML患者的长期预后，因此对于NPM1突变的AML患者，必须重新审视共突变谱以确定可能受益于allo-HSCT的最佳人群。在这项研究中，我们对2018年10月至2022年12月在我们中心诊断为NPM1突变（不包括急性早幼粒细胞白血病）的新诊断成人AML患者进行了回顾性分析，重点探讨了NPM1突变AML患者共突变特征的治疗和预后意义。

Patients who received at least one complete course of induction therapy were included in the further outcome analysis. Table S1 provi.

接受至少一个完整诱导治疗疗程的患者被纳入进一步的结果分析。表S1提供。

Data availability

数据可用性

The data are not publicly available, owing to ethics considerations and privacy restriction, but can be requested from the corresponding author if necessary.

由于道德考虑和隐私限制，这些数据无法公开获得，但如有必要，可以向通讯作者索取。

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Download referencesFundingThis work was supported in part by National Natural Science Foundation of China (82370162); Natural Science Foundation of Zhejiang Province, China (LY23H080005); Key R&D Program of Zhejiang (2024C03162) and the Fundamental Research Funds for the Central Universities (226-2022-00003).Author informationAuthor notesThese authors contributed equally: Yiyi Yao, Yile Zhou, Nanfang Zhuo.Authors and AffiliationsDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, PR ChinaYiyi Yao, Yile Zhou, Nanfang Zhuo, Wanzhuo Xie, Haitao Meng, Yinjun Lou, Liping Mao, Hongyan Tong, Jiejing Qian, Min Yang, Wenjuan Yu, De Zhou, Jie Jin & Huafeng WangZhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, 310000, Zhejiang, PR ChinaYiyi Yao, Yile Zhou, Nanfang Zhuo, Wanzhuo Xie, Haitao Meng, Yinjun Lou, Liping Mao, Hongyan Tong, Jiejing Qian, Min Yang, Wenjuan Yu, De Zhou, Jie Jin & Huafeng WangZhejiang Provincial Clinical Research Center for Hematological disorders, Hangzhou, 310000, Zhejiang, PR ChinaHongyan Tong, Jie Jin & Huafeng WangZhejiang University Cancer Center, Hangzhou, 310000, Zhejiang, PR ChinaHongyan Tong, Jie Jin & Huafeng WangAuthorsYiyi YaoView 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自然科学基金（82370162）的部分支持；浙江省自然科学基金（LY23H080005）；浙江省重点研发项目（2024C03162）和中央大学基础研究基金（226-2022-00003）。作者信息作者注意到这些作者做出了同样的贡献：姚一毅，周一乐，南方卓。作者和所属单位浙江大学医学院第一附属医院血液科，杭州，310003，浙江，中华人民共和国易义姚，易乐周，南方卓，谢万卓，孟海涛，娄银军，毛立平，童红艳，钱洁晶，杨敏阳，余文娟，周德锦，王华峰浙江省造血系统恶性肿瘤重点实验室，浙江杭州，310000，中华人民共和国易义姚，易乐周，南方卓，谢万卓，孟海涛，娄银军，毛立平，童红艳，钱洁晶，杨敏娟，余文娟，周德，Jie Jin＆Huafeng Wang浙江省血液病临床研究中心，杭州，310000，浙江，中华人民共和国洪岩Tong，Jie Jin＆Huafeng Wang浙江大学癌症中心，杭州，310000，浙江，中华人民共和国洪岩Tong，Jie Jin＆Huafeng Wang作者Yiyi YaoView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsYY and HW designed the study, collected and analyzed the data, and wrote the first draft of the manuscript. YZ, NZ, WX, HM, YL, LM, HT, JQ, MY, WY, and DZ collected and analyzed the data, and reviewed the manuscript. JJ and HW read and reviewed the manuscript.

PubMed Google ScholarContributionsYY和HW设计了这项研究，收集并分析了数据，并撰写了手稿的初稿。YZ，NZ，WX，HM，YL，LM，HT，JQ，MY，WY和DZ收集并分析了数据，并审阅了手稿。JJ和HW阅读并审阅了手稿。

HW accessed and verified the data, and provided administrative support. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.Corresponding authorCorrespondence to.

硬件访问并验证了数据，并提供了管理支持。所有作者都可以完全访问研究中的所有数据，并对提交出版物的决定负有最终责任。对应作者对应。

Huafeng Wang.Ethics declarations

王华峰。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethics approval and consent to participate

道德批准和同意参与

This study was approved by local ethics committees and was conducted in accordance with the Declaration of Helsinki. All patients signed written informed consent.

这项研究得到了当地伦理委员会的批准，并根据《赫尔辛基宣言》进行。所有患者均签署了书面知情同意书。

Consent for publication

同意出版

All patients signed informed consent and also consented to the publication of these data.

所有患者均签署了知情同意书，并同意发布这些数据。

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Reprints and permissionsAbout this articleCite this articleYao, Y., Zhou, Y., Zhuo, N. et al. Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with NPM1-mutated de novo acute myeloid leukemia.

转载和许可本文引用本文Yao，Y.，Zhou，Y.，Zhuo，N。等人。共突变景观及其对新诊断的NPM1突变的新发急性髓细胞白血病成年患者的预后影响。

Blood Cancer J. 14, 118 (2024). https://doi.org/10.1038/s41408-024-01103-wDownload citationReceived: 18 April 2024Revised: 08 July 2024Accepted: 11 July 2024Published: 22 July 2024DOI: https://doi.org/10.1038/s41408-024-01103-wShare 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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