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MYELODYSPLASTIC SYNDROME

Prevalence of UBA1 mutations in MDS/CMML patients with systemic inflammatory and auto-immune disease

Leukemia volume 35, pages 2731–2733 (2021)Cite this article

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Systemic inflammatory and auto-immune diseases (SIAD) are observed in 25% of patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemias (CMML), and include a wide spectrum of clinical manifestations encompassing dysregulated activation of both innate and adaptive immunity [1]. In a cohort of 85 MDS/CMML patients with SIAD, we recently found that TET2, IDH1/2, and SRSF2 mutations were more prevalent in MDS/CMML patients with SIAD compared with 319 MDS/CMML patients without SIAD. We also found a correlation between naive/memory T-cell imbalance, defects in immune checkpoint receptors expression and TET2/IDH mutational status, suggesting that these last mutations may play a role in a common pathogenesis of the two disorders [2].

Recently, somatic mutations in UBA1, a gene involved in the initiation of cellular ubiquitin signaling, have been described in patients with adult-onset inflammatory diseases, including relapsing polychondritis (RP) and Sweet syndrome (SwS), defining a novel disease called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome [3]. In this seminal paper as in a subsequent work by Bourbon et al. [4], about 25% of patients also had MDS. However, the prevalence of UBA1 mutations in MDS and CMML patients remains unknown, as is its implication in all MDS/CMML associated inflammatory disorders. The frequency and specificity of cell vacuoles in this context has also been recently disputed [5]. We sought to explore the prevalence of UBA1 mutations and the characteristics of mutated patients in our cohort of MDS/CMML with SIAD.

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Fig. 1: Hematopoietic Precursors morphology with vacuoles on bone marrow smears from MDS patients.

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Author notes

  1. These authors contributed equally: Lin-Pierre Zhao, Berenice Schell.

Authors and Affiliations

  1. Université de Paris, Department of Hematology, Hôpital Saint-Louis, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France

    Lin-Pierre Zhao, Marie Sébert, Raphaël Itzykson, Pierre Fenaux & Lionel Adès

  2. Université de Paris, Institut de Recherche Saint-Louis, EMiLy, INSERM U1160, Paris, France

    Lin-Pierre Zhao, Berenice Schell, Maxime Boy, Valéria Bisio, Antoine Toubert & Nicolas Dulphy

  3. Université de Paris, Laboratory of Hematology, AP-HP, Hôpital Saint-Louis, Paris, France

    Berenice Schell, Rathana Kim, Pierre Lemaire, Stephanie Mathis, Lise Larcher, Clémentine Chauvel, Mohamed Bedis Dhouaieb & Emmanuelle Clappier

  4. Université de Paris, Institut de Recherche Saint-Louis, INSERM U944, Paris, France

    Marie Sébert, Lise Larcher, Raphaël Itzykson & Emmanuelle Clappier

  5. Laboratory of Hematology, Centre Hospitalier Universitaire Lille, Lille, France

    Claude Preudhomme & Alice Marceau-Renaut

  6. INSERM Lille, University of Lille, Lille, France

    Claude Preudhomme & Alice Marceau-Renaut

  7. Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Saint-Antoine, AP-HP, Paris, France

    Arsène Mekinian & Olivier Fain

  8. Laboratoire d’Immunologie et d’Histocompatibilité, Hôpital Saint-Louis, AP-HP, F-75010, Paris, France

    Antoine Toubert & Nicolas Dulphy

Authors
  1. Lin-Pierre Zhao
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  21. Lionel Adès
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Contributions

LPZ analyzed the clinical data; BS, RK, M Boy and EC performed experiments, analyzed biological results and made figures; AM, LA, MS, OF and PF provided clinical information and took care of the patients; AT, CC, LL, M Bedis, ND, PL, and SM provided scientific expertise; LPZ, BS, PF, LA and EC wrote the manuscript. All the authors critically reviewed the manuscript and gave final approval for submission.

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Correspondence to Lionel Adès.

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Zhao, LP., Schell, B., Sébert, M. et al. Prevalence of UBA1 mutations in MDS/CMML patients with systemic inflammatory and auto-immune disease. Leukemia 35, 2731–2733 (2021). https://doi.org/10.1038/s41375-021-01353-8

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