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MYELODYSPLASTIC NEOPLASM

Germline CHEK2 mutations in patients with myeloid neoplasms

Leukemia volume 38, pages 908–911 (2024)Cite this article

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While germline alterations in many genes have been recognized as predisposition factors in the development of myeloid neoplasms (MN) [1, 2], distinguishing sporadic or inherited myeloid malignancies is crucial for individual or familial genetic counseling, and therapeutic management. Wider use of large genomic profiling has revealed several pathogenic germline variants in cancer susceptibility genes [3], and for some of them, the causality and risk to develop a MN remains unknown or unclear. CHEK2 protein is a cell-cycle checkpoint kinase controlling DNA repair, cell-cycle arrest and apoptosis, which can lead to genomic instability and tumorigenesis when altered [4]. Several studies have addressed the role of deleterious germline CHEK2 variants (CHEK2mutGL) in various solid cancers without trivial interpretations and conclusions [5]. In patients with MN, CHEK2mutGL is poorly explored and has not been included in recently updated WHO [1] 2022 while added to the list of germline predisposing genes in the ELN 2022 classification [6].

In our study, we aim to establish the prevalence of CHEK2mutGL, to describe associated features and to report prognosis impact of CHEK2 mutational status in MN.

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Fig. 1: Patient selection and P/LP CHEK2 variants identified.
Fig. 2: Clinical and biological features of patients with a P/LP CHEK2 germline variant.

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Acknowledgements

We thank the patients and their families, primary investigators and biologists of the AZA-PLUS study. The authors thank the Saint-Louis and CHU de Lille Molecular Hematology laboratories. The authors thank all the physicians, nurses and all those who work for taking care of the patients The author thank the “groupe francophone des myélodysplasies (GFM)”, who supported this study.

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Author notes

  1. These authors contributed equally: Lucie Freiman, Lise Larcher.

Authors and Affiliations

  1. Institut de Recherche Saint-Louis (IRSL), Université Paris Cité, 75010, Paris, France

    Lucie Freiman, Lise Larcher, Matthieu Duchmann, Lionel Adès, Pierre Fenaux, Jean Soulier, Nicolas Duployez, Emmanuelle Clappier & Marie Sébert

  2. Clinical Hematology Departments, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France

    Lucie Freiman, Emmanuel Raffoux, Lionel Adès, Pierre Fenaux & Marie Sébert

  3. Hematology Laboratory, Saint-Louis Hospital, APHP, Paris, France

    Lise Larcher, Giulia Tueur, Nadia Vasquez, Mélanie Da Costa, Matthieu Duchmann, Jean Soulier, Nicolas Duployez & Emmanuelle Clappier

  4. INSERM U944/CNRS UMR7212, Paris, France

    Lise Larcher, Matthieu Duchmann, Lionel Adès, Pierre Fenaux, Jean Soulier, Emmanuelle Clappier & Marie Sébert

  5. Hematology Laboratory, Unité 1277-Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER), Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, Lille, France

    Nicolas Duployez

Authors
  1. Lucie Freiman
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  2. Lise Larcher
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  10. Jean Soulier
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  11. Nicolas Duployez
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  13. Marie Sébert
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Contributions

Contribution: MS, LF, LL, ND, and EC designed the study; EC, LL, GT, NV, MDC, MD, ND and JS provided and analyzed biological data; ER, LA, PF, MS and LF managed patients and provided clinical data; LF, LL, MS, and ND analyzed data and wrote the manuscript; and all authors reviewed the manuscript.

Corresponding author

Correspondence to Marie Sébert.

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Freiman, L., Larcher, L., Tueur, G. et al. Germline CHEK2 mutations in patients with myeloid neoplasms. Leukemia 38, 908–911 (2024). https://doi.org/10.1038/s41375-024-02179-w

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