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MYELODYSPLASTIC NEOPLASM

What role for somatic mutations in systemic inflammatory and autoimmune diseases associated with myelodysplastic neoplasms and chronic myelomonocytic leukemias?

Leukemia volume 37, pages 1186–1190 (2023)Cite this article

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About 25% of myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukemias (CMML) are associated with systemic inflammatory and autoimmune diseases (SIAD) [1], generally diagnosed almost concomitantly, but mechanisms underlying this association remain poorly known. Recently, somatic mutations in UBA1 gene were demonstrated as causal event of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome (MIM #301054) [2], a severe autoinflammatory condition frequently associated with MDS.

In this paper, we hypothesize a common pathophysiology for the association between MDS/CMML and SIAD, with potential therapeutic perspectives, especially for the use of azacytidine (AZA).

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Fig. 1: Clinical spectrum of systemic inflammatory and autoimmune diseases (SIAD) associated with myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukemias (CMML).
Fig. 2: Proposed pathophysiological model of MDS/CMML associated with Systemic Inflammatory and Autoimmune Diseases (SIAD), at least in the case of TET2/IDH (and possibly SRSF2) mutation.
Fig. 3: Proposed provisional therapeutic decision tree for MDS/CMML-associated SIAD.

Data availability

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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Authors and Affiliations

  1. Université Paris Cité, APHP, Hôpital Saint-Louis, Hématologie Seniors, Paris, France

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

  2. INSERM UMR 1160, Institut de Recherche Saint-Louis, Paris, France

    Lin-Pierre Zhao, Marion Espéli, Karl Balabanian & Nicolas Dulphy

  3. Sorbonne Université, APHP, Hôpital Saint-Antoine, service de Médecine Interne, Paris, France

    Arsène Mékinian & Olivier Fain

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LPZ and PF wrote the manuscript. LPZ designed the figures. All the authors critically reviewed the design and the content of the manuscript.

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Correspondence to Lin-Pierre Zhao.

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Zhao, LP., Sébert, M., Mékinian, A. et al. What role for somatic mutations in systemic inflammatory and autoimmune diseases associated with myelodysplastic neoplasms and chronic myelomonocytic leukemias?. Leukemia 37, 1186–1190 (2023). https://doi.org/10.1038/s41375-023-01890-4

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