Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome

Int J Hematol. 2023 Oct;118(4):494-502. doi: 10.1007/s12185-023-03598-8. Epub 2023 Apr 17.


VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a new disease entity with autoinflammatory disorders (AID) driven by somatic variants in UBA1 that frequently co-exists with myelodysplastic syndromes (MDS). Clinicopathological and molecular features of Japanese cases with VEXAS-associated MDS remain elusive. We previously reported high prevalence of UBA1 variants in Japanese patients with relapsing polychondritis, in which 5 cases co-occurred with MDS. Here, we report clinicopathological and variant profiles of these 5 cases and 2 additional cases of MDS associated with VEXAS syndrome. Clinical characteristics of these cases included high prevalence of macrocytic anemia with marked cytoplasmic vacuoles in myeloid/erythroid precursors and low bone marrow (BM) blast percentages. All cases were classified as low or very low risk by the revised international prognostic scoring system (IPSS-R). Notably, 4 out of 7 cases showed significant improvement of anemia by treatment with prednisolone (PSL) or cyclosporin A (CsA), suggesting that an underlying inflammatory milieu induced by VEXAS syndrome may aggravate macrocytic anemia in VEXAS-associated MDS. Targeted deep sequencing of blood samples suggested that MDS associated with VEXAS syndrome tends to involve a smaller number of genes and lower risk genetic lesions than classical MDS.

Keywords: DNMT3A; MDS; PSL; TET2; VEXAS syndrome.

MeSH terms

  • Bone Marrow / pathology
  • East Asian People* / genetics
  • Humans
  • Mutation
  • Myelodysplastic Syndromes* / ethnology
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / therapy
  • Risk


  • UBA1 protein, human

Supplementary concepts

  • VEXAS syndrome
  • Japanese people