Spectrum of clonal trajectories of UBA1 mutant clones. Patients with the VEXAS syndrome have increased risk of MDS and plasma cell dyscrasias (monoclonal gammopathy of undetermined significance [MGUS] and multiple myeloma). Additional somatic mutations in typical drivers of clonal hematopoiesis (DNMT3A and TET2) and/or other genes enriched/specific for MDS contribute to clonal progression toward overt malignancy. A staging based on conventional clinical parameters (cytopenia and bone marrow dysplasia) is complicated by the inflammatory environment. CH, clonal hematopoiesis.