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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, page 1943 (2023)Cite this article

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We thank Suarez et al. for their correspondence to our paper published in the April 2023 issue of Leukemia [1], where in particular they disagree on “incorporating UBA1 mutation in the systematic molecular analysis of all MDS”. In fact, our Figure 3 suggests performing systematic UBA1 screening in MDS associated with systemic autoimmune/autoinflammatory diseases (SIAD), not in all MDS patients. We believe UBA1 screening is relevant in those patients because i/ the prevalence of VEXAS syndrome is significant in this subgroup (12% in selected MDS with SIAD [2]), while up to 50% of VEXAS patients meet WHO criteria [3] for MDS in the largest series [4]; ii/ early UBA1 mutation identification may help to prevent diagnosis wandering, and frequent and severe VEXAS-related complications such as thrombosis [5], and iii/ although treatment guidelines in VEXAS syndrome are lacking and most evidence relies on retrospective studies, therapeutic options including biotherapies, ruxolitinib [6], azacytidine (AZA) [7] and allogeneic stem cell transplantation (allo-SCT) [1, 8] have shown some efficacy, hence our suggested treatment algorithm in Figure 3. Of note, in lower-risk MDS patients, the presence of UBA1 mutation may be an additional argument to indicate more aggressive therapeutic interventions including AZA and possibly allo-SCT. Of course, treatment of VEXAS syndrome with or without MDS may evolve with the potential advent of more targeted therapies.

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References

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Authors and Affiliations

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

    Lin-Pierre Zhao & Pierre Fenaux

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

    Lin-Pierre Zhao

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  1. Lin-Pierre Zhao
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  2. Pierre Fenaux
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Correspondence to Lin-Pierre Zhao.

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Zhao, LP., Fenaux, P. What role for somatic mutations in systemic inflammatory and autoimmune diseases associated with myelodysplastic neoplasms and chronic myelomonocytic leukemias?. Leukemia 37, 1943 (2023). https://doi.org/10.1038/s41375-023-01990-1

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