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MYELODYSPLASTIC NEOPLASM

Clinical impact of genetic alterations including germline DDX41 mutations in MDS/low-blast count AML patients treated with azacitidine-based regimens

Leukemia volume 38, pages 918–922 (2024)Cite this article

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Myelodysplastic syndromes (MDS) patients stratification was based on International Prognostic Scoring System (IPSS) and Revised IPSS (IPSS-R). Recently, a model integrating the mutational status of 31 genes (IPSS-M) refined overall survival (OS) and acute myeloid leukemia (AML) free survival (AMLFS) predictions [1,2,3,4]. The large number of parameters required in IPSS-M may limit its applicability and other groups reported that genetic stratification with smaller gene panel could efficiently predict outcome [5]. Only few studies evaluated the predictive impact of IPSS-M in MDS patients treated with hypomethylating agents (HMA) including azacitidine (AZA), the only available drugs for higher-risk (HR) MDS.

Germline DDX41 mutations (DDX41MutGL) represent the most frequent genetic predisposition to myeloid neoplasms (MN), accounting for 3–8% adult patients [6,7,8]. Several studies reported DDX41MutGL MN as specific entities [6, 7], with favorable outcome in cohorts receiving heterogeneous treatments [6, 8] or intensive chemotherapy [7]. Thus, we sought to investigate the prognostic impact of genetic alterations including DDX41MutGL in a large cohort of MDS/low-blast (LB) count AML patients treated with AZA-based regimens in two prospective randomized trials.

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Fig. 1: Molecular predictor of overall survival and characteristics of DDX41MutGL patients in the overall cohort.
Fig. 2: Prognostic impact of DDX41MutGL in AZA-PLUS cohort.

Data availability

Data sharing requests should be sent to Matthieu Duchmann (matthieu.duchmann@aphp.fr).

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Acknowledgements

We thank all investigators from the Groupe Français des Myélodysplasies (GFM). This study was supported by the GFM. MD was supported by the Bettencourt Schueller Foundation (CCA-INSERM-Bettencourt).

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Author notes

  1. These authors jointly supervised this work: Nicolas Duployez, Matthieu Duchmann.

Authors and Affiliations

  1. Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France

    Marie Sébert, Pierre Fenaux, Emmanuelle Clappier, Lionel Adès, Nicolas Duployez & Matthieu Duchmann

  2. Hematology Department, Saint Louis Hospital, AP-HP, Paris, France

    Marie Sébert, Lucie Freiman, Pierre Fenaux & Lionel Adès

  3. Groupe Francophone des Myelodysplasies, Paris, France

    Marie Sébert, Agnès Guerci, Pierre Peterlin, Sylvain Thépot, Odile Beyne-Rauzy, Sophie Park, Thomas Cluzeau, Fatiha Chermat, Pierre Fenaux & Lionel Adès

  4. Biostatistics Department, Saint Louis Hospital, AP-HP, Paris, France

    Cendrine Chaffaut & Sylvie Chevret

  5. Hematology Department, CHU Brabois Vandoeuvre, Nancy, France

    Agnès Guerci

  6. Hematology Department, Nantes University Hospital, Nantes, France

    Pierre Peterlin

  7. Hematology Department, Angers University Hospital, Angers, France

    Sylvain Thépot

  8. Hematology Department, CHU de Toulouse, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France

    Odile Beyne-Rauzy

  9. Hematology Department, Grenoble University Hospital, Grenoble, France

    Sophie Park

  10. Hematology Department, Nice University Hospital, Nice, France

    Thomas Cluzeau

  11. Hematology Laboratory, Unité 1277-Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER), Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Lille, France

    Claude Preudhomme & Nicolas Duployez

  12. Hematology Laboratory, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France

    Emmanuelle Clappier, Nicolas Duployez & Matthieu Duchmann

Authors
  1. Marie Sébert
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Contributions

MS, ND and MD designed the study. LF, CC, AG, PP, ST, OBR, SP, TC, FC, PF, SC, LA managed patients and clinical data. CP, EC and ND performed biological analyses. MD performed statistical analyses. MS, LA, ND and MD wrote the manuscript. All authors reviewed and approved the manuscript.

Corresponding authors

Correspondence to Marie Sébert or Matthieu Duchmann.

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The authors declare no competing interests.

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Sébert, M., Freiman, L., Chaffaut, C. et al. Clinical impact of genetic alterations including germline DDX41 mutations in MDS/low-blast count AML patients treated with azacitidine-based regimens. Leukemia 38, 918–922 (2024). https://doi.org/10.1038/s41375-024-02180-3

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