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STEM CELL TRANSPLANTATION

Impact of TP53 variants and germline mutations on allogeneic stem cell transplantation outcomes in acute myeloid leukemia and myelodysplastic neoplasms

Leukemia volume 39, pages 2292–2296 (2025)Cite this article

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TP53-mutated myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are typically characterized by complex cytogenetic abnormalities and resistance to intensive chemotherapy [1, 2]. Allogeneic stem cell transplantation (allo-HSCT) remains the only curative option, yet the outcomes of germline versus somatic TP53-mutated AML/MDS under allo-HSCT remain poorly explored. Moreover, the prognostic impact of TP53 mutations (TP53mut) across different domains is not well characterized. Additionally, the effects of missense versus truncating mutations [3, 4] and the prognostic significance of multi-hit TP53 status in AML/MDS remain controversial [5, 6]. Given the clinical and biological heterogeneity of TP53 mutations, this multi-center retrospective study aims to delineate the differences between germline and somatic TP53mut to refine disease trajectories and optimize transplant strategies.

Somatic mutations were identified by next-generation sequencing, while germline TP53 variants were confirmed using oral mucosa testing. Germline TP53mut carriers received allo-HSCT from related donors negative for the corresponding variant. Pre-transplant MRD was assessed by multiparameter flow cytometry (MFC) on bone marrow, with MRD positivity defined as ≥0.01% leukemic-associated immunophenotypes.

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Fig. 1: Study schema, oncoplot and survival outcomes of TP53-mutated AML/MDS cohort.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the patients who contributed to this study. This work was supported by grants from the National Key R&D Program of China, Stem Cell and Translation Research (grant nos. 2022YFA1103500), and the National Natural Science Foundation of China (grant nos. 82470212).

Author information

Author notes

  1. These authors contributed equally: Yeqian Zhao, Weijie Cao, Jimin Shi, Yang Cao, Ying Lu.

Authors and Affiliations

  1. Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China

    Yeqian Zhao, Jimin Shi, Yi Luo, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, He Huang & Yanmin Zhao

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Yeqian Zhao, Jimin Shi, Yi Luo, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, He Huang & Yanmin Zhao

  3. Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China

    Yeqian Zhao, Jimin Shi, Yi Luo, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, He Huang & Yanmin Zhao

  4. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Weijie Cao

  5. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Yang Cao

  6. Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo, China

    Ying Lu & Lieguang Chen

  7. Department of Hematology, Ningbo First Hospital, Ningbo, Zhejiang, China

    Guifang Ouyang

  8. Department of Hematology and Hematopoietic Stem Cell Transplant Center, Zhejiang Provincial People’s Hospital, Hangzhou, China

    Jianping Lan & Xiaolu Song

  9. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Yi Chen

  10. Department of Hematology, The Second Affiliate Hospital of Nanchang University, Nanchang, China

    Li Yu

  11. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China

    Xiaodong Mo

  12. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaoxia Hu

Authors
  1. Yeqian Zhao
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  2. Weijie Cao
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  3. Jimin Shi
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  4. Yang Cao
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  5. Ying Lu
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  6. Yi Luo
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  8. Lieguang Chen
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  20. Xiaoxia Hu
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  21. He Huang
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  22. Yanmin Zhao
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Contributions

YM Zhao, H Huang, XX Hu and XD Mo: conceptualization, supervision, writing— reviewing and editing; YQ Zhao, WJ Cao, JM Shi and Y Cao: data curation, writing—original draft preparation, visualization; Y Lu, Y Luo, GF Ouyang, LG Chen, JP Lan, XL Song, Y Chen, L Yu, J Yu, XY Lai, LZ Liu, HR Fu, YS Ye and LX Yang: data curation and supervision.

Corresponding authors

Correspondence to Xiaodong Mo, Xiaoxia Hu, He Huang or Yanmin Zhao.

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Competing interests

The authors declare no competing interests.

Ethical approval

The study was approved by the Ethics Review Committee of each center.

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Informed consent was obtained from all participants, including consent for the use of tissue samples where applicable.

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Zhao, Y., Cao, W., Shi, J. et al. Impact of TP53 variants and germline mutations on allogeneic stem cell transplantation outcomes in acute myeloid leukemia and myelodysplastic neoplasms. Leukemia 39, 2292–2296 (2025). https://doi.org/10.1038/s41375-025-02672-w

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