Splicing together the origins of MDS-RS

Abstract

In this issue of Blood, Mortera-Blanco et al provide definitive evidence of the origin of myelodysplastic syndrome (MDS) with ring sideroblasts (RS) by tracing mutations in the splicing factor SF3B1 back to phenotypic hematopoietic stem cells (HSC) with multilineage potential. This study shows not only that SF3B1 mutations are early events in MDS and identifiable in myeloid lineage but also that SF3B1 lesions are detectable in pro-B cells. The authors also present a patient-derived mouse xenograft model that recapitulates MDS with RS phenotype from multipotent SF3B1-mutant HSCs derived from MDS-RS patients.1