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ACUTE MYELOID LEUKEMIA

Mutations in DEAD/H-box helicase 11 correlate with increased relapse risk in adults with acute myeloid leukaemia with normal cytogenetics

Leukemia volume 38, pages 223–225 (2024)Cite this article

Subjects

People with acute myeloid leukaemia with normal cytogenetics (CN-AML) have diverse outcomes explained in part by different mutation topographies [1,2,3]. DDX11 encodes ChlR1, an ATP-dependent DNA helicase important in DNA damage repair and other cell processes which maintaining genomic integrity [4]. Bi-allelic DDX11 mutations result in a rare autosomal recessive disorder, Warsaw breakage syndrome [5]. Somatic DDX11 mutations are reportedly associated with poor survival in myelodysplastic syndrome (MDS) and lymphoid cancers [6]. However, there are few data on the impact of DDX11 mutations on outcomes in AML.

We interrogated data from 1358 consecutive subjects with newly-diagnosed AML at Peking University People’s Hospital from May, 2010 to December, 2019. AML was diagnosed by histology, immunology, cytogenetics and genetic abnormalities as described [7]. Inclusion criteria included: (1) age 16–65 years; (2) normal cytogenetics; and (3) achieving histological complete remission after induction therapy. Four hundred twenty-three subjects were eligible (Supplementary Fig. 1). Details of induction and consolidation therapy are as reported [8]. Transplant eligible subjects had donor searches during induction therapy. After the 2nd consolidation course, eligible subjects with a potential donor and physicians discussed risks and benefits of a transplant versus continuing consolidation chemotherapy according to co-variates such as risk stratification, measurable residual disease (MRD)-test results, economics and subject preference. Based on these discussions 193 of 423 eligible subjects (46%) received a transplant after a median of 4 (range 2–6) courses of consolidation chemotherapy as described [8]. The study was approved by the Ethics Committee of Peking University People’s Hospital and written informed consent was received from all subjects complaint with the precepts of the Declaration of Helsinki.

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Fig. 1: DDX11 mutations correlate with CIR and RFS.

Data availability

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

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Acknowledgements

RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research.

Funding

Supported by grants from National Natural Science Foundation of China [Grant 82100169], National Natural Science Foundation of China [Grant 81930004], Major Programme of the National Natural Science Foundation of China [Grant 82293630], National Key Research and Development Program of China [No. 2022YFA1103300] and the Beijing Municipal Natural Science Foundation [Grant 7192213].

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  1. These authors contributed equally: Ya-Lan Zhou, Ming-Yue Zhao.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing, China

    Ya-Lan Zhou, Ming-Yue Zhao, Hao Jiang, Qian Jiang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang & Guo-Rui Ruan

  2. Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK

    Robert Peter Gale

  3. Acornmed Biotechnology Co., Ltd., Tianjin, China

    Li-Xia Liu, Jia-Yue Qin, Shan-Bo Cao & Feng Lou

  4. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Xiao-Jun Huang

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  1. Ya-Lan Zhou
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Contributions

G-RR, X-JH and RPG designed the project and prepared the typescript. Y-LZ, M-YZ, S-BC, FL, L-XL and J-YQ performed the experiments and statistical analyses. HJ, QJ, L-PX, and X-HZ provided clinical data. All authors read and approved the final typescript and agreed to submit it for publication.

Corresponding authors

Correspondence to Xiao-Jun Huang or Guo-Rui Ruan.

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Competing interests

RPG is a consultant to Antengene Biotech LLC; Medical Director, FFF Enterprises Inc.; A speaker for Janssen Pharma and Hengrui Pharma; Board of Directors: Russian Foundation for Cancer Research Support and Scientific Advisory Board, StemRad Ltd.

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Zhou, YL., Zhao, MY., Gale, R.P. et al. Mutations in DEAD/H-box helicase 11 correlate with increased relapse risk in adults with acute myeloid leukaemia with normal cytogenetics. Leukemia 38, 223–225 (2024). https://doi.org/10.1038/s41375-023-02085-7

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