Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond

Lancet Haematol. 2024 Feb;11(2):e160-e167. doi: 10.1016/S2352-3026(23)00375-7.


The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The mere observation of vacuolated progenitor cells is not specific to VEXAS syndrome; in this Viewpoint, we point out the causes to be considered in this situation. Vacuoles, in particular, can be observed in individuals with wild-type UBA1 and with persistent inflammatory features or myelodysplastic syndromes. However, several clues support the diagnosis of VEXAS syndrome in the presence of vacuolated bone marrow progenitors: a high number of vacuolated progenitors and of vacuoles per cell, the predominance of vacuoles in early rather than late progenitors, and the vacuolisation of both myeloid and erythroid progenitors with predominance of myeloid ones. Some criteria derived from these observations have been proposed with great diagnostic performances. However, the absence or a low proportion of vacuolated cells should not prevent UBA1 gene sequencing.

Publication types

  • Review

MeSH terms

  • Bone Marrow*
  • Humans
  • Mutation
  • Myelodysplastic Syndromes*
  • Skin Diseases, Genetic*
  • Vacuoles

Supplementary concepts

  • VEXAS syndrome