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ACUTE MYELOID LEUKEMIA

Clinically associated genomic landscape of pediatric non-Down Syndrome acute megakaryoblastic leukemia in Chinese patients

Leukemia volume 39, pages 2533–2537 (2025)Cite this article

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Acute megakaryoblastic leukemia (AMKL) accounts for 4%–15% of newly diagnosed pediatric acute myeloid leukemia (AML) [1]. Pediatric AMKL contains two major subtypes: AMKL associated with Down Syndrome (DS-AMKL) and AMKL occurring independently of Down Syndrome (non-DS-AMKL). Unlike DS-AMKL, driven predominantly by trisomy 21 and GATA1 mutations, non-DS-AMKL has greater genomic heterogeneity and worse clinical outcomes [2, 3]. Next-generation sequencing studies have identified key oncogenic drivers in non-DS-AMKL, including RBM15::MKL1, CBFA2T3::GLIS2, NUP98::KDM5A, and KMT2A rearrangements [4,5,6]. Nonetheless, the genetic foundations of 20% of non-DS-AMKL cases remain unknown, posing a major challenge for advancing precision medicine and developing effective targeted therapies.

We performed a comprehensive transcriptomic analysis of Chinese pediatric non-DS-AMKL. We enrolled 117 patients with non-DS-AMKL between November 2009 and October 2022 at Shanghai Children’s Medical Center (SCMC) (Supplementary Table 1). The clinical characteristics of Chinese pediatric non-DS-AMKL cases closely resembled those of non-AMKL pediatric AML cases (Supplementary Table 2) [7], with the exception of a significantly younger median age (1.3 vs. 6.5 years, p < 0.001, Fisher’s exact test). Transcriptome sequencing (RNA-seq) was performed on 58 diagnostic samples from this cohort and were integrated with the RNA-seq profiles we published previously [7]. Ultimately, we analyze transcriptomic data from 100 pediatric non-DS-AMKL cases (Supplementary Table 3).

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Fig. 1: Genomic landscape of pediatric non-DS-AMKL and its clinical relevance.
Fig. 2: Network-based drug sensitivity prediction in AMKL.

Data availability

The RNA-seq data generated in this study have been deposited in the Genome Sequence Archive of the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences under accession number HRA003012. The RNA-seq data from previous study is under accession number of HRA000789. These data can be accessed at https://ngdc.cncb.ac.cn/gsa-human.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (82170155 to SS, U24A20678 to YL and 32400517 to XC), the Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province (2022ZQNZD011 to YL), the Shanghai Municipal Education Commission Research and Innovation Program (2021-01-07-00-02-E00091 to SS), the Foundation of National Research Center for Translational Medicine at Shanghai (NRCTM(SH)-2019-04 to SS), the Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics (20dz2260900 to YL).

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Author notes

  1. These authors contributed equally: Kefei Wu, Hui Liu, Wenting Hu.

Authors and Affiliations

  1. Key Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Kefei Wu, Hui Liu, Wenting Hu, Yuhan Liu, Yanjing Tang, Jiaoyang Cai, Xiang Wang, Xiaoxiao Chen, Yixiao Mo, Ting Liu, Yangyang Xie, Changcheng Chen, Zhuo Wang, Jing Chen, Jing Chen, Benshang Li, Xiaolong Chen, Yu Liu & Shuhong Shen

  2. Biomedical Data Science Center, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Wenyan Wu, Bowen Cui, Han Wang, Shuang Zhao, Huiying Sun, Ying Zhong, Jianan Rao, Rongrong Fan, Ying Wang, Ronghua Wang, Yuanlu Huang, Qiaoqiao Shi, Xiaolong Chen & Yu Liu

  3. CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China

    Yong Wang & Lan Wang

  4. Guizhou Medical University, Guiyang, China

    Yuanlu Huang

  5. Fujian Children’s Hospital, Fujian Branch of Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Fuzhou, China

    Yu Liu

  6. Hainan Branch of Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, China

    Yu Liu

Authors
  1. Kefei Wu
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  2. Hui Liu
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Contributions

KW and HL analyzed transcriptomic and functional data. KW, HL, YW, and LW performed functional studies. BC, WW, SZ, HW, HS, YZ, YW, QS, RF, RW, and YH performed analyzed the genomic and transcriptomic data. KW and BC conducted statistical analysis. WH, YuhanL, YT, JC, XC, YM, YX, XW, CC, ZW, Jing-C, Jing C, and BL collected clinical samples and information. WW, JR, WH, and TL provided sequencing data and supported bioinformatics pipelines. SS, YL, and XC designed and supervised the study. KW, XC, YL, and SS wrote the manuscript.

Corresponding authors

Correspondence to Xiaolong Chen, Yu Liu or Shuhong Shen.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The research was approved by the Ethics Committee at Shanghai Children’s Medical Center. Informed consents were obtained from parents for all patients. All methods were performed in accordance with the relevant guidelines and regulations.

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Wu, K., Liu, H., Hu, W. et al. Clinically associated genomic landscape of pediatric non-Down Syndrome acute megakaryoblastic leukemia in Chinese patients. Leukemia 39, 2533–2537 (2025). https://doi.org/10.1038/s41375-025-02741-0

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